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Clinical and radiological features of posterior reversible encephalopathy syndrome in patients with pre-eclampsia and eclampsia
Clinical Radiology xxx (2017) 1e9
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Clinical and radiological features of posterior reversible encephalopathy syndrome in patients with pre-eclampsia and eclampsia X.Y. Dong, C.B. Bai, J.F. Nao* Department of Neurology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, China
art icl e i nformat ion Article history: Received 25 January 2017 Received in revised form 26 May 2017 Accepted 6 June 2017
AIM: To analyse and summarise clinical and radiological features among patients with posterior reversible encephalopathy syndrome (PRES), to assess related factors with eclampsia and pre-eclampsia, and to compare the different factors between cytotoxic and vasogenic oedema among PRES patients. MATERIALS AND METHODS: The clinical and radiological findings of 237 pre-eclamptic or eclamptic patients with neurological symptoms were evaluated retrospectively. Multiple logistic regression analyses were performed to compare the differences among these parameters. RESULTS: Seventy-six patients (32.07%) were diagnosed with PRES. Multiple logistic regression indicated that seizure (odds ratio [OR], 2.760; 95% confidence interval [CI]: 1.087 e7.011; p¼0.033), visual disturbances (OR¼2.062 95%CI, 1.033e4.115; p¼0.004), multiple production history (OR¼3.637; 95% CI: 1.068e8.228; p¼0.002) were independent risk factors for PRES. PRESþ (OR¼3.217; 95%CI, 1.346e7.686; p¼0.009), Visual disturbances (OR¼4.283; 95% CI: 1.843e9.953; p¼0.001) had strong association with eclampsia. Visual disturbances (OR¼7.200; 95% CI: 2.116e24.496; p¼0.002) had strong correlation with eclampsia among PRESþ patients. Visual disturbances (OR¼2.947; 95% CI: 1.135e7.648; p¼0.026) were independently related to cytotoxic oedema. CONCLUSIONS: Nearly one-third of pre-eclampsia or eclampsia patients with neurological symptoms have PRES. Visual disturbances, seizure, multiple production history are independent risk factors for PRES. Visual disturbances have a strong association with eclampsia whether patients have PRES or not. Visual disturbances are independently related to cytotoxic oedema among PRESþ patients. Ó 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction
* Guarantor and correspondent: J.F. Nao, Department of Neurology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, China. Tel.:þ86 024 18940256567; Fax: þ86 024 18940256567. E-mail address: [email protected] (J.F. Nao).
Posterior reversible encephalopathy syndrome (PRES), a condition first described by Hinchey et al. in 1996, is a clinicoradiological entity characterised by a collection of signs and symptoms: impaired consciousness, visual changes, acute-onset seizures, headache, nausea, and vomiting, and focal neurological signs.1 Magnetic resonance
http://dx.doi.org/10.1016/j.crad.2017.06.009 0009-9260/Ó 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Dong XY, et al., Clinical and radiological features of posterior reversible encephalopathy syndrome in patients with pre-eclampsia and eclampsia, Clinical Radiology (2017), http://dx.doi.org/10.1016/j.crad.2017.06.009
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imaging (MRI) evaluation of patients with PRES reveals bilateral and symmetrical vasogenic oedema involving the cortical and subcortical regions of the occipital and parietal lobes, although some patients present with atypical distributions including the anterior cerebral lobes, brain stem, cerebellum, and basal ganglia (BG).2e6 The factors predisposing to PRES in patients with pre-eclampsia and eclampsia are still under debate, and the MRI findings of some patients demonstrate cytotoxic rather than the more typical vasogenic oedema.7 Pre-eclampsia and eclampsia, conditions that predispose to PRES, are characterised by clinical hypertension, peripheral oedema, proteinuria, and sometimes seizure during pregnancy; pre-eclampsia and eclampsia have a similar mechanism to PRES. The mechanism by which PRES occurs is still not clear, but there are three popular theories: hypertension-induced vasoconstriction, ischaemia and vasospasm, and endothelial injury.2,8e12 Patients without hypertension can still develop PRES.4 The reported prognosis of pre-eclampsia or eclampsia patients with PRES is relatively favourable. In the majority of patients, PRES is completely reversible with or without restricted cytotoxic oedema.13 The aim of the present study was to assess the incidence and risk factors of PRES in a large sample of patients with pre-eclampsia or eclampsia, and to evaluate clinical and radiological features among PRES patients. Related factors with eclampsia or pre-eclampsia were also assessed and the different factors between cytotoxic and vasogenic oedema were compared among PRES patients.
Materials and methods
patients who were not admitted to the hospital when their neurological symptoms began. Mean arterial pressure (MAP) was also investigated at: two-thirds of the DBP and one-third of the SBP. Data were collected on clinical parameters (patient age, SBP, DBP, mean blood pressure [MBP]), routine laboratory investigations (haemoglobin, platelet count, D-dimer level), neurological symptoms (headache, seizures, visual disturbances), and MRI findings.
Neuroimaging MRI using a 3 T magnet was used in all patients. The standard protocol consisted of axial T1- and T2-weighted sequences, fluid-attenuated inversion recovery (FLAIR) sequences, and diffusion-weighted imaging (DWI). Apparent diffusion coefficient (ADC) maps were calculated on a pixelby-pixel basis. The mean ADC values for each region of interest were calculated automatically. All MRI results were evaluated by two neuroimaging professors blinded to the clinical information. Patients were divided into two groups according to MRI findings, the PRESþ group and the PRESe group, depending on the presence of high signal intensity on T2-weighted imaging and FLAIR. The PRES group was further divided into those patients with cytotoxic oedema and those with vasogenic oedema: a high DWI signal combined with a decreased ADC indicated the presence of cytotoxic oedema, while a low DWI signal with increased ADC indicated vasogenic oedema. Patients’ clinical features, imaging lesions, and laboratory data were collected and compared to determine whether there were any differing factors related to these two different types of oedema. The involved lesions were summarised and compared between PRES patients with pre-eclampsia versus eclampsia.
Patients and study protocol
Treatment and follow-up
A hospital-based retrospective review of women with neurological symptoms who were diagnosed with preeclampsia or eclampsia between 2010 and 2015 was conducted. All participants provided written informed consent prior to inclusion in the study. The diagnostic criterion for pre-eclampsia was a first instance of blood pressure (BP) 140 mmHg or a diastolic BP (DBP) 90 mmHg occurring after 20 weeks of gestation together with proteinuria, >300 mg/24 h; eclampsia was defined as the occurrence of seizures that could not be attributed to other causes in women with pre-eclampsia.14 The diagnostic criteria for PRES were: (1) acute or subacute onset of at least one neurological symptom such as headache, dizziness, seizure, visual disturbance, or impaired consciousness; (2) MRI showing focal bilateral oedema of the cortex and subcortical white matter; (3) complete resolution of most or all clinical symptoms and radiological findings during pregnancy or post-partum; (4) no other disease that could have similar manifestations such as acute stroke, cerebral venous-sinus thrombosis, viral encephalitis, and immune disorder associated encephalopathy. The BP value was recorded, if documented, at the onset of neurological symptoms or at the time of admission for those
All patients were given magnesium sulphate for seizure prophylaxis, as 20 ml of a 25% magnesium sulphate solution diluted in a 10% glucose solution, given intravenously over 5e10 minutes. Patients were monitored for signs of toxicity: absent patellar reflex, respiratory rate <16/min, or urine output <25 ml/h.15 Patients with a SBP 160 mmHg, DBP 110 mmHg, or MAP 140 mmHg received intravenous labetalol: 20 mg as a first dose, followed by 40 mg if not effective within 10 minutes, then 80 mg every 10 minutes to a maximum total dose of 240 mg.14 In patients with eclampsia, seizures were controlled with 10 mg diazepam; if this was ineffectual, they received phenytoin, 100 mg every 8 or 12 hours. Thirty patients underwent emergency termination of pregnancy for insufficient seizure control. All PRES patients were followed for 1 month for the persistence of neurological symptoms and for follow-up MRI findings.
Data analysis Statistical analyses were conducted using Statistical Package for the Social Sciences, version 17.0. Continuous data were reported as the mean standard deviation;
Please cite this article in press as: Dong XY, et al., Clinical and radiological features of posterior reversible encephalopathy syndrome in patients with pre-eclampsia and eclampsia, Clinical Radiology (2017), http://dx.doi.org/10.1016/j.crad.2017.06.009
X.Y. Dong et al. / Clinical Radiology xxx (2017) 1e9
discrete data were reported as the frequency and percentage. Student’s t-test was applied for continuous variables, and Fisher’s exact test was applied for discrete variables. On multivariate analysis, multiple logistic regression was used to analyse the risk factors related to PRES, associated factors with pre-eclampsia and eclampsia among PRESþ patients, respectively, and to compare related factors between cytotoxic and vasogenic oedema among PRESþ patients. A pvalue of <0.05 was considered to indicate a statistically significant difference.
Results A total of 237 obstetric patients diagnosed pre-eclampsia or eclampsia with neurological symptoms were included. All patients underwent cranial MRI within 48 hours of symptom onset. A total of 76 patients (32.07%) were diagnosed with PRES. In the PRESþ group, the neurological symptoms recorded were headache in 64 patients (84.2%), visual disturbance in 36 patients (47.4%), and seizure in 20 patients (26.3%); 31 patients (40.8%) were multiparous. In the PRESe group, headache was present in 139 patients (86.3%), visual disturbance in 42 patients (26.1%), and seizure in 11 patients (6.8%); 41 patients (25.5%) were multiparous. The factors with statistically significant differences between the PRESþ and PRESe groups were age (p¼0.017), seizure (p<0.001), visual disturbances (p¼0.002), and multiple production history (p¼0.018). The age of patients in the PRESþ group (28.24 5.88 years) was younger than the of the PRESe group (30.11 5.47 years; p¼0.017), and there was a significant difference in D-dimer levels (p<0.001) and platelet counts (p<0.001; Table 1). Blood pressure, although higher in the PRES group, had no significant correlation with the presence of PRES (Fig 1). Three factors were independently related to PRES on multilogistic regression: seizure (odds ratio [OR], 2.760; 95% confidence interval [CI]: 1.087e7.011; p¼0.033), visual disturbances (OR¼2.062 95% CI:
Table 1 Demographic, clinical, and laboratory data among posterior reversible encephalopathy syndrome negative (PRESe) and positive (PRESþ) patients.
a
Parameter
PRESe (n¼161)
PRESþ (n¼76)
p-Value
Age (years) Headache Visual disturbances Seizure Multiple production history SBP (mmHg) DBP (mmHg) MBP (mmHg) Platelet count (109/l) Haemoglobin (g/l) D-dimers (mg/l) Creatinine (mmol/l)
30.115.47 139 (86.3%) 42 (26.1%) 11 (6.83%) 41 (25.5%)
28.245.88 64 (84.2%) 36 (47.4%) 20 (26.3%) 31 (40.8%)
0.017a 0.665 0.002a 0.000a 0.018a
155.9123.97 100.8215.22 119.1617.36 171.2260.15 114.8219.06 971.671156.94 89.67318.90
161.1321.68 101.9312.66 121.7114.47 130.9562.75 112.7822.45 1758.181605.68 76.9322.67
0.108 0.580 0.267 0.000a 0.469 0.000a 0.728
Statistically significant at p<0.05. SBP, systolic blood pressure; DBP, diastolic blood pressure; MBP, mean blood pressure.
3
1.033e4.115; p¼0.004), multiple production history (OR¼3.637; 95% CI: 1.068e8.228; p¼0.002). In the comparison of pre-eclampsia and eclampsia patients, PRESþ (p¼0.000), visual disturbances (p¼0.000), seizure (p¼0.000), platelet count (p¼0.008) were statistically significant between the two groups (Table 2). PRESþ (OR¼3.217; 95% CI: 1.346e7.686; p¼0.009), visual disturbances (OR¼4.283; 95% CI: 1.843e9.953; p¼0.001) had strong association with eclampsia. Seventy-six patients were diagnosed with PRES: 20 with eclampsia and 56 with pre-eclampsia. When comparing pre-eclampsia and eclampsia, visual disturbances (p¼0.000), seizure (p¼0.000), and platelet count (p¼0.029) were different between the two groups. Age, headache, multiple production history, BP, haemoglobin, D dimers were not statistically significant (Table 3). After multilogistic regression, visual disturbances (OR¼7.200; 95% CI: 2.116e24.496; p¼0.002) had a strong association with eclampsia among PRESþ patients. A total of 30 patients (39.47%) with PRES demonstrated cytotoxic oedema (Fig 2), while 46 PRES patients had vasogenic oedema (Fig 3). Visual disturbances (p¼0.024), multiple production history (p¼0.040), and D-dimer level (p¼0.044) were statistically different between the two groups. No other parameters, including haemoglobin and platelet count, age, SBP, DBP, or MBP, or related lesions were statistically different between the two groups (Table 4). After multi-logistic regression, only the presence of visual disturbances (OR¼2.947; 95% CI: 1.135e7.648; p¼0.026) was independently associated with cytotoxic oedema. The occipital and parietal lobes were the most commonly involved regions (Fig 4). In patients with eclampsia, the parietal lobe was most commonly involved (18/20), followed by the occipital lobe (17/20); in the pre-eclampsia group, the occipital lobe was most frequently involved (45/56), followed by the parietal lobe (42/56). The BG, brain stem, and cerebellum were also frequently involved regions; BG involvement was especially common in the preeclampsia group (28/56; Fig 5); however, no statistically significant difference could be found in the location of lesions between patients with pre-eclampsia and eclampsia. All 76 patients with PRES were followed for 1 month after delivery. All patients underwent follow-up MRI and it was demonstrated that their neuroimaging manifestations were reversible.
Discussion Pre-eclampsia is one of the most serious disorders of pregnancy. Characterised by hypertension and proteinuria, it usually develops after 20 weeks of gestation.16 If one or more convulsions complicate pre-eclampsia, the patient is diagnosed with eclampsia. Pre-eclampsia or eclampsia can cause central nervous system disturbances such as subarachnoid haemorrhage, acute cerebral infarction, cerebral haemorrhage, and cerebral venous sinus thrombosis.17 All of these complications may have long-term sequelae. PRES, a common neurological complication reported in patients
Please cite this article in press as: Dong XY, et al., Clinical and radiological features of posterior reversible encephalopathy syndrome in patients with pre-eclampsia and eclampsia, Clinical Radiology (2017), http://dx.doi.org/10.1016/j.crad.2017.06.009
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Figure 1 BP comparison between PRESe and PRESþ.
with eclampsia and pre-eclampsia, involves neurological symptoms such as headache, dizziness, nausea, vomiting, visual disturbances, convulsions, and even coma; however, patients usually have a good neurological outcome.18 Malignant and rapid onset of hypertension, eclampsia, immunosuppressive therapy, transplantation, circulating toxic mediators, sepsis, and autoimmune conditions are commonly identified as potential inducements. PRES may occur as a result of either breakdown of cerebral autoregulation or destruction of the bloodebrain barrier, leading
Table 2 Demographic, clinical, and laboratory data among pre-eclampsia and eclampsia patients.
Age (year) PRESþ Seizure Headache Visual disturbances Multiple production history SBP (mmHg) DBP (mmHg) MBP (mmHg) Platelet count (109/l) Haemoglobin (g/l) D-dimers (mg/l) Creatinine (mmol/l) a
Pre-eclampsia (n¼206)
Eclampsia (n¼31)
p-Value
29.735.58 56 (27.2%) 0 (0%) 173 (84%) 57 (27.7%) 62 (30.1%)
29.406.55 20 (64.5%) 31 (100%) 30 (96.8%) 21 (67.7%) 10 (32.3%)
0.127 0.000a 0.000a 0.059 0.000a 0.808
157.3923.97 100.7414.55 119.6216.79 162.5360.90 113.7519.34 1162.891300.89 85.42281.91
158.9018.93 104.0613.48 122.3414.21 130.2275.19 116.9225.29 1629.231699.84 86.6629.70
0.737 0.233 0.393 0.008a 0.416 0.076 0.981
Statistically significant at p<0.05. SBP, systolic blood pressure; DBP, diastolic blood pressure; MBP, mean blood pressure; PRESþ, posterior reversible encephalopathy syndrome positive.
to vasogenic oedema or endothelial dysfunction.19e23 In the present study, the correlation between pre-eclampsiaeeclampsia and PRES was studied. Although no statistical difference in BP was found, the PRESþ group did have slightly higher BP values. Although dynamic changes in the present patients could not be tested, other studies have indicated that PRES in eclamptic patients can develop without a significant rise in BP.12 “Relative hypertension” may be a crucial factor for the development of PRES.
Table 3 Demographic, clinical, and laboratory data among pre-eclampsia and eclampsia among posterior reversible encephalopathy syndrome patients.
Age (years) Headache Visual disturbances Seizure Multiple production history SBP (mmHg) DBP (mmHg) MBP (mmHg) Platelet count (109/l) Haemoglobin (g/l) D-dimers (mg/l) Creatinine (mmol/l)
Eclampsia (n¼20)
Pre-eclampsia (n¼56)
p-Value
29.406.55 17 (85%) 16 (80%) 20 (100%) 9 (45%)
27.825.63 47 (84%) 20 (35.7%) 0 (0%) 22 (39.3%)
0.306 0.910 0.000a 0.000a 0.656
156.6519.83 102.5015.16 120.5515.33 104.7970.51 111.9723.16 1683.501907.83 85.4432.27
162.7322.25 101.7311.79 122.0714.29 140.2957.56 113.0622.40 1784.861501.85 73.8917.47
0.284 0.818 0.691 0.029a 0.853 0.810 0.05
a Statistically significant at p<0.05. SBP, systolic blood pressure; DBP, diastolic blood pressure; MBP, mean blood pressure.
Please cite this article in press as: Dong XY, et al., Clinical and radiological features of posterior reversible encephalopathy syndrome in patients with pre-eclampsia and eclampsia, Clinical Radiology (2017), http://dx.doi.org/10.1016/j.crad.2017.06.009
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Figure 2 MRI images of the brain of a 23-year-old woman with preeclampsia. (a) FLAIR MRI shows hyperintensity within the bilateral parietal lobe. (b) DWI shows restricted hyperintensity in left parietal lobe. (c) ADC image shows hyperintensity in the bilateral parietal regions but relative hypointensity in the corresponding restricted diffusion region.
In the present study, visual disturbances, seizure, and multiple production history were independent risk factors that relate to PRES. Visual disturbance as a clinical symptom included cortical blindness, blurred vision, and aethomma. Although the pathogenesis of PRES is not yet fully clarified, disturbance of the cerebral autoregulation mechanism and impairment of endothelial function has been widely accepted. In PRES cases, direct toxic effects on endothelium or vessel expansion by rising BP may comparatively weaken the effect of myogenic autoregulation. Therefore, neurogenic mechanisms take over the regulation of cerebral perfusion. In this way, posterior circulation areas become more sensitive to BP elevation owing to a relative lack of sympathetic nerves. Limits of cerebral autoregulation pass beyond the normal levels of blood pressure and vasogenic oedema occurs in the posterior circulation, especially in the occipital lobes and parietal lobes.24,25 In the present study, the occipital and parietal lobes, as visual centres, were the most commonly affected regions. This explains why visual disturbances are more common in PRES groups and are an independent risk factor for PRES. Bilateral and symmetrical vasogenic oedema or cytotoxic oedema involving the cortical and subcortical regions of the occipital and parietal lobes are most commonly seen in PRES.18,19 Similarly, seizure as a clinical symptom is thought to result from fluid in the cortex and white matter. Cerebral oedema was present in all of the present cases with
seizures. Seizure reflects fluid extravasation and oedema across the cortex, subcortex, and white matter, which is caused by cerebral hyper-perfusion pressure.22,23 In the present study, multiparity was found to be another independent risk factor with PRES. Kari et al.26 found that patients with pre-eclampsia and eclampsia experience an excessive inflammatory response: leukocyte activation, and pro-coagulant and anti-angiogenic factors together lead to vascular endothelial damage and dysfunction, which could be another pathomechanism for PRES. Multiparity together with pre-eclampsia or eclampsia may produce an excessive inflammatory response, which causes endothelium dysfunction leading to PRES. When comparing eclampsia with pre-eclampsia patients, PRES occurred in over half of the eclampsia patients (64.5%), which was much higher than pre-eclampsia patients (27.2%). Multiple regression showed that PRES was as independent related factor for eclampsia. PRES, as a result of either breakdown of cerebral autoregulation or destruction of the bloodebrain barrier, leads to vasogenic oedema or endothelial dysfunction. Cerebral oedema might induce seizure in women with pregnancy, especially cortical or subcortical oedema, which ultimately leads to the occurrence of eclampsia.27,28 Cooray et al.29 found visual symptoms can arise from different parts of the visual pathway, it occurs in approximately 25% of pre-eclamptic and 19e45% of eclamptic
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Figure 3 MRI images of the brain of a 20-year-old woman with antepartum eclampsia. (a) T2-weighted imaging shows oedema involving the bilateral occipital regions. (b) ADC and (c) DWI show involvement of the region with vasogenic oedema.
Table 4 Demographic, clinical, laboratory, and radiological data with vasogenic oedema and cytotoxic oedema among posterior reversible encephalopathy syndrome patients.
a
Parameter
Vasogenic oedema (N ¼ 46)
Cytotoxic oedema (N ¼ 30)
p-Value
Age (years) Headache Visual disturbances Seizure Multiple production history Related lesions Frontal Temporal Parietal Occipital Brainstem Cerebellum Basal ganglion SBP (mmHg) DBP (mmHg) MBP (mmHg) Platelet count (109/l) Haemoglobin B (g/l) D-dimer (mg/l)
29.206.14 46 (100%) 17 (37%) 10 (21.7%) 23 (50%)
26.775.22 30 (100%) 19 (63.3%) 10 (33.3%) 8 (26.7%)
0.078 1.000 0.024a 0.262 0.040a
21 (45.7%) 9 (19.6%) 34 (73.9%) 39 (84.8%) 4 (8.7%) 7 (15.2%) 24 (52.2%) 160.9620.25 101.9812.12 121.7013.67 122.8255.17 108.8217.76 2057.021815.57
14 (46.7%) 6 (20%) 26 (86.7%) 24 (80%) 2 (6.7%) 7 (23.3%) 15 (50%) 161.4024.06 101.8713.66 121.7315.87 143.4172.07 118.8427.40 1299.971092.68
0.931 0.963 0.183 0.588 0.748 0.372 0.853 0.931 0.970 0.991 0.163 0.057 0.044a
Statistically significant at p<0.05. SBP, systolic blood pressure; DBP, diastolic blood pressure; MBP, mean blood pressure.
women, and comprises blurry vision, diplopia, amaurosis fugax, photopsia, and homonymous haemianopsia. This concurs with the present study, as a higher incident of visual disturbance was found in eclampsia patients (67.7%) than pre-eclampsia patients (27.7%), and logistic regression analyses indicate that visual disturbance is an independent factor for eclampsia. Eclampsia patients sustain intense organ hypertransfusion and endothelial dysfunction, particularly occurring in the posterior region, as a result they are more likely to have visual disturbance. The ratio of visual disturbance among eclampsia patients (80%) is significantly higher than that of patients with preeclampsia (35.7%) among PRES patients, and multiple regression shows visual disturbance is an independent related factor for eclampsia. Combined with the discussion above, visual disturbances have a strong association with eclampsia whether patients present with PRES or not. Two major theories are proposed to clarify the pathomechanism of PRES: cytotoxic oedema theory and vasogenic oedema theory. The cytotoxic oedema theory argues that cytotoxic oedema is associated with vasoconstriction and local cerebral ischaemic necrosis. The vasogenic oedema theory supports that elevated vasogenic BP overcomes cerebral autoregulation, leading to cerebral vasodilatation and vasogenic cerebral oedema. The relation of DWI
Please cite this article in press as: Dong XY, et al., Clinical and radiological features of posterior reversible encephalopathy syndrome in patients with pre-eclampsia and eclampsia, Clinical Radiology (2017), http://dx.doi.org/10.1016/j.crad.2017.06.009
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Figure 4 T2-weighted MRI images of a 26-year-old woman with antepartum eclampsia showing involvement of bilateral BG (a) occipital and (b) parietal regions.
Figure 5 Distribution of lesions in MRI. Please cite this article in press as: Dong XY, et al., Clinical and radiological features of posterior reversible encephalopathy syndrome in patients with pre-eclampsia and eclampsia, Clinical Radiology (2017), http://dx.doi.org/10.1016/j.crad.2017.06.009
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findings to ADC can help differentiate vasogenic oedema from cytotoxic oedema.22,30 The present study concurs with previous studies of vasogenic oedema, but the cytotoxic oedema in PRES may not be the same as in cerebrovascular ischaemia. By investigating the neuroimaging of patients with PRES, some cytotoxic oedema (using DWI criteria) occurred in the centre of large areas of vasogenic oedema, i.e., occurred as transient cytotoxic oedema. As the vasogenic oedema resolves, cytotoxic oedema eases at the same time; this is not the same with cytotoxic oedema caused by acute cerebral infarction where there are long-term sequelae. In the present study, visual disturbances were more common in patients with cytotoxic oedema (63.3%) than in those with vasogenic oedema (37%), and visual disturbances were found to be independent related factors for cytotoxic oedema in PRESþ patients. This high frequency of cytotoxic oedema present in pre-eclampsia or eclampsia may be caused by endothelial damage, which is the most crucial factor for PRES in pre-eclampsia and eclampsia patients.9,17 A high level of endothelin, a potential vasoconstrictor peptide, can lead to reversible narrowing of large and medium-sized cerebral arteries, which may be responsible for vasospasm.16 Severe hypertension also promotes cerebral overregulation, vasoconstriction, infarction, and cytotoxic oedema formation.18 Posterior areas, such as visual centre, are easily influenced by endothelial damage, vasospasm, and vasoconstriction, which may impair visual pathways and lead to visual disturbances. Other possible aetiologies including: haematological malignancies,31 post-streptococcal glomerulonephritis,32 polyarteritis nodosa,33 intravenous cyclophosphamide therapy,34 and acute intermittent porphyria35 could also lead to PRES. The aetiology, pathogenesis, and prognosis of PRES are associated with the primary disease. Early diagnosis and prompt treatment of the primary disease could improve the prognosis. The present study is the largest to include both eclampsia and pre-eclampsia patients who underwent MRI for PRES evaluation; however, the present study has limitations. First, this was a single-centre, retrospective study, and selection bias may be present. Second, because of the short follow-up period (1 month), the long-term prognosis of patients with pre-eclampsia and eclampsia and PRES could not be determined. In conclusion, PRES is present in 32.07% of patients with pre-eclampsia and eclampsia at Shengjing Hospital of China Medical University. Visual disturbances, seizure, and multiparity were independent risk factors for PRES. Visual disturbances have strong association with eclampsia whether patients have PRES or not. Visual disturbances are also relevant to cytotoxic oedema among PRESþ patients. The parietal and occipital lobes are the most commonly involved regions in PRES; there is no difference in the regions involved between pre-eclampsia and eclampsia patients. PRES can be alleviated with prompt diagnosis and intensive treatment.
References 1. Hinchey J, Chaves C, Appignani B, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996;334:494e500. 2. Karampekios SK, Contopoulou E, Basta M, et al. Hypertensive encephalopathy with predominant brain stem involvement: MRI findings. J Hum Hypertens 2004;18:133e4. 3. Choh NA, Jehangir M, Rasheed M, et al. Involvement of the cervical cord and medulla in posterior reversible encephalopathy syndrome. Ann Saudi Med 2011;31:90e2. 4. Chen TY, Lee HJ, Wu TC, et al. MR imaging findings of medulla oblongata involvement in posterior reversible encephalopathy syndrome secondary to hypertension. AJNR Am J Neuroradiol 2009;30:755e7. 5. Ono Y, Manabe Y, Hamakawa Y, et al. Localized lesions on MRI in a case of hypertensive brainstem encephalopathy. Intern Med 2005;44:1002e5. 6. Ekawa Y, Shiota M, Tobiume T, et al. Reversible posterior encephalopathy syndrome accompanying eclampsia: correct diagnosis using preoperative MRI. Tohoku J Exp Med 2012;226:55e8. 7. McKinney AM, Short J, Truwit CL, et al. Posterior reversible encephalopathy syndrome: incidence of atypical regions of involvement and imaging findings. AJR Am J Roentgenol 2007;189:904e12. 8. Staykov D, Schwab S. Posterior reversible encephalopathy syndrome. J Intensive Care Med 2012;27:11e24. 9. Lee VH, Wijdicks EF, Manno EM, et al. Clinical spectrum of reversible posterior leukoencephalopathy syndrome. Arch Neurol 2008;65:205e10. 10. Mueller-Mang C, Mang T, Pirker A, et al. Posterior reversible encephalopathy syndrome: do predisposing risk factors make a difference in MRI appearance? Neuroradiology 2009;51:373e83. 11. Many A, Hubel CA, Roberts JM. Hyperuricemia and xanthine oxidase in pre-eclampsia, revisited. Am J Obstet Gynecol 1996;174:288e91. 12. Ay H, Buonanno FS, Schaefer PW, et al. Posterior leukoencephalopathy without severe hypertension: utility of diffusion-weighted MRI. Neurology 1998;51:1369e76. 13. Alaa W, Laila M, Moustafa MR, et al. Posterior reversible encephalopathy syndrome (PRES): restricted diffusion does not necessarily mean irreversibility. Pol J Radiol 2015;80:210e6. 14. Report of the national high blood pressure education program working group on high blood pressure in pregnancy. Am J Obstet Gynecol 2000;183:S1e22. 15. Duley L. Magnesium sulphate regimens for women with eclampsia: messages from the Collaborative Eclampsia Trial. Br J Obstet Gynaecol 1996;103:103e5. 16. Mutter WP, Karumanchi SA. Molecular mechanisms of pre-eclampsia. Microvasc Res 2008;75:1e8. 17. Singh RR, Ozyilmaz N, Waller S, et al. A study on clinical and radiological features and outcome in patients with posterior reversible encephalopathy syndrome (PRES). Eur J Pediatr 2014;173:1225e31. 18. Kutlesi c MS, Kutlesi c RM, Koratevi c GP. Posterior reversible encephalopathy syndrome in eclamptic patients: neuroradiological manifestation, pathogenesis and management. Med Pregl 2015;68:53e8. 19. Bartynski WS. Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical features. AJNR Am J Neuroradiol 2008;29:1036e42. 20. Turner JA. Diagnosis and management of pre-eclampsia: an update. Int J Women Health 2010;2:327e37. 21. Noori M, Donald AE, Angelakopoluou A, et al. Prospective study of placental angiogenic factors and maternal vascular function before and after pre-eclampsia and gestational hypertension. Circulation 2010;122:478e87. 22. Schaefer PW, Buonanno FS, Gonzalez RG, et al. Diffusion-weighted imaging discriminates between cytotoxic and vasogenic oedema in a patient with eclampsia. Stroke 1997;28:1082e5. 23. Junewar V, Verma R, Sankhwar PL, et al. Neuroimaging features and predictors of outcome in eclamptic encephalopathy: a prospective observational study. AJNR Am J Neuroradiol 2014;35:1728e34. 24. Vanina F, Alessandro B, Michela B, et al. Magnetic resonance imaging in posterior reversible encephalopathy syndrome: report of three cases and review of literature. Arch Gynecol Obstet 2005;271:79e85.
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X.Y. Dong et al. / Clinical Radiology xxx (2017) 1e9 25. Roth C, Ferbert A. Posterior reversible encephalopathy syndrome: is there a difference between pregnant and non-pregnant patients? Eur Neurol 2009;62:142e8. 26. Flo Kari, Blix Egil S, Husebekk Anne, et al. A longitudinal study of maternal endothelial function, inflammatory response and uterine artery blood flow during the second half of pregnancy. Acta Obstet Gynecol Scand 2016;95:225e32. 27. Jaremo P, Lindahl TL, Lennmarken C, et al. The use of platelet density and volume measurements to estimate the severity of pre-eclampsia. Eur J Clin Invest 2000;30:1113e8. 28. Sibai BM, Schneider JM, Morrison JC, et al. The late postpartum eclampsia controversy. Obstet Gynecol 1980;55:74e8. 29. Cooray SD, Edmonds SM, Tong S, et al. Characterization of symptoms immediately preceding eclampsia. Obstet Gynecol 2011;118:995e9. 30. Doelken M, Lanz S, Rennert J, et al. Differentiation of cytotoxic and vasogenic oedema in a patient with reversible posterior leukoence-
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Clinical and radiological features of posterior reversible encephalopathy syndrome in patients with pre-eclampsia and eclampsia X.Y. Dong, C.B. Bai, J.F. Nao* Department of Neurology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, China
art icl e i nformat ion Article history: Received 25 January 2017 Received in revised form 26 May 2017 Accepted 6 June 2017
AIM: To analyse and summarise clinical and radiological features among patients with posterior reversible encephalopathy syndrome (PRES), to assess related factors with eclampsia and pre-eclampsia, and to compare the different factors between cytotoxic and vasogenic oedema among PRES patients. MATERIALS AND METHODS: The clinical and radiological findings of 237 pre-eclamptic or eclamptic patients with neurological symptoms were evaluated retrospectively. Multiple logistic regression analyses were performed to compare the differences among these parameters. RESULTS: Seventy-six patients (32.07%) were diagnosed with PRES. Multiple logistic regression indicated that seizure (odds ratio [OR], 2.760; 95% confidence interval [CI]: 1.087 e7.011; p¼0.033), visual disturbances (OR¼2.062 95%CI, 1.033e4.115; p¼0.004), multiple production history (OR¼3.637; 95% CI: 1.068e8.228; p¼0.002) were independent risk factors for PRES. PRESþ (OR¼3.217; 95%CI, 1.346e7.686; p¼0.009), Visual disturbances (OR¼4.283; 95% CI: 1.843e9.953; p¼0.001) had strong association with eclampsia. Visual disturbances (OR¼7.200; 95% CI: 2.116e24.496; p¼0.002) had strong correlation with eclampsia among PRESþ patients. Visual disturbances (OR¼2.947; 95% CI: 1.135e7.648; p¼0.026) were independently related to cytotoxic oedema. CONCLUSIONS: Nearly one-third of pre-eclampsia or eclampsia patients with neurological symptoms have PRES. Visual disturbances, seizure, multiple production history are independent risk factors for PRES. Visual disturbances have a strong association with eclampsia whether patients have PRES or not. Visual disturbances are independently related to cytotoxic oedema among PRESþ patients. Ó 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction
* Guarantor and correspondent: J.F. Nao, Department of Neurology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, China. Tel.:þ86 024 18940256567; Fax: þ86 024 18940256567. E-mail address: [email protected] (J.F. Nao).
Posterior reversible encephalopathy syndrome (PRES), a condition first described by Hinchey et al. in 1996, is a clinicoradiological entity characterised by a collection of signs and symptoms: impaired consciousness, visual changes, acute-onset seizures, headache, nausea, and vomiting, and focal neurological signs.1 Magnetic resonance
http://dx.doi.org/10.1016/j.crad.2017.06.009 0009-9260/Ó 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
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imaging (MRI) evaluation of patients with PRES reveals bilateral and symmetrical vasogenic oedema involving the cortical and subcortical regions of the occipital and parietal lobes, although some patients present with atypical distributions including the anterior cerebral lobes, brain stem, cerebellum, and basal ganglia (BG).2e6 The factors predisposing to PRES in patients with pre-eclampsia and eclampsia are still under debate, and the MRI findings of some patients demonstrate cytotoxic rather than the more typical vasogenic oedema.7 Pre-eclampsia and eclampsia, conditions that predispose to PRES, are characterised by clinical hypertension, peripheral oedema, proteinuria, and sometimes seizure during pregnancy; pre-eclampsia and eclampsia have a similar mechanism to PRES. The mechanism by which PRES occurs is still not clear, but there are three popular theories: hypertension-induced vasoconstriction, ischaemia and vasospasm, and endothelial injury.2,8e12 Patients without hypertension can still develop PRES.4 The reported prognosis of pre-eclampsia or eclampsia patients with PRES is relatively favourable. In the majority of patients, PRES is completely reversible with or without restricted cytotoxic oedema.13 The aim of the present study was to assess the incidence and risk factors of PRES in a large sample of patients with pre-eclampsia or eclampsia, and to evaluate clinical and radiological features among PRES patients. Related factors with eclampsia or pre-eclampsia were also assessed and the different factors between cytotoxic and vasogenic oedema were compared among PRES patients.
Materials and methods
patients who were not admitted to the hospital when their neurological symptoms began. Mean arterial pressure (MAP) was also investigated at: two-thirds of the DBP and one-third of the SBP. Data were collected on clinical parameters (patient age, SBP, DBP, mean blood pressure [MBP]), routine laboratory investigations (haemoglobin, platelet count, D-dimer level), neurological symptoms (headache, seizures, visual disturbances), and MRI findings.
Neuroimaging MRI using a 3 T magnet was used in all patients. The standard protocol consisted of axial T1- and T2-weighted sequences, fluid-attenuated inversion recovery (FLAIR) sequences, and diffusion-weighted imaging (DWI). Apparent diffusion coefficient (ADC) maps were calculated on a pixelby-pixel basis. The mean ADC values for each region of interest were calculated automatically. All MRI results were evaluated by two neuroimaging professors blinded to the clinical information. Patients were divided into two groups according to MRI findings, the PRESþ group and the PRESe group, depending on the presence of high signal intensity on T2-weighted imaging and FLAIR. The PRES group was further divided into those patients with cytotoxic oedema and those with vasogenic oedema: a high DWI signal combined with a decreased ADC indicated the presence of cytotoxic oedema, while a low DWI signal with increased ADC indicated vasogenic oedema. Patients’ clinical features, imaging lesions, and laboratory data were collected and compared to determine whether there were any differing factors related to these two different types of oedema. The involved lesions were summarised and compared between PRES patients with pre-eclampsia versus eclampsia.
Patients and study protocol
Treatment and follow-up
A hospital-based retrospective review of women with neurological symptoms who were diagnosed with preeclampsia or eclampsia between 2010 and 2015 was conducted. All participants provided written informed consent prior to inclusion in the study. The diagnostic criterion for pre-eclampsia was a first instance of blood pressure (BP) 140 mmHg or a diastolic BP (DBP) 90 mmHg occurring after 20 weeks of gestation together with proteinuria, >300 mg/24 h; eclampsia was defined as the occurrence of seizures that could not be attributed to other causes in women with pre-eclampsia.14 The diagnostic criteria for PRES were: (1) acute or subacute onset of at least one neurological symptom such as headache, dizziness, seizure, visual disturbance, or impaired consciousness; (2) MRI showing focal bilateral oedema of the cortex and subcortical white matter; (3) complete resolution of most or all clinical symptoms and radiological findings during pregnancy or post-partum; (4) no other disease that could have similar manifestations such as acute stroke, cerebral venous-sinus thrombosis, viral encephalitis, and immune disorder associated encephalopathy. The BP value was recorded, if documented, at the onset of neurological symptoms or at the time of admission for those
All patients were given magnesium sulphate for seizure prophylaxis, as 20 ml of a 25% magnesium sulphate solution diluted in a 10% glucose solution, given intravenously over 5e10 minutes. Patients were monitored for signs of toxicity: absent patellar reflex, respiratory rate <16/min, or urine output <25 ml/h.15 Patients with a SBP 160 mmHg, DBP 110 mmHg, or MAP 140 mmHg received intravenous labetalol: 20 mg as a first dose, followed by 40 mg if not effective within 10 minutes, then 80 mg every 10 minutes to a maximum total dose of 240 mg.14 In patients with eclampsia, seizures were controlled with 10 mg diazepam; if this was ineffectual, they received phenytoin, 100 mg every 8 or 12 hours. Thirty patients underwent emergency termination of pregnancy for insufficient seizure control. All PRES patients were followed for 1 month for the persistence of neurological symptoms and for follow-up MRI findings.
Data analysis Statistical analyses were conducted using Statistical Package for the Social Sciences, version 17.0. Continuous data were reported as the mean standard deviation;
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X.Y. Dong et al. / Clinical Radiology xxx (2017) 1e9
discrete data were reported as the frequency and percentage. Student’s t-test was applied for continuous variables, and Fisher’s exact test was applied for discrete variables. On multivariate analysis, multiple logistic regression was used to analyse the risk factors related to PRES, associated factors with pre-eclampsia and eclampsia among PRESþ patients, respectively, and to compare related factors between cytotoxic and vasogenic oedema among PRESþ patients. A pvalue of <0.05 was considered to indicate a statistically significant difference.
Results A total of 237 obstetric patients diagnosed pre-eclampsia or eclampsia with neurological symptoms were included. All patients underwent cranial MRI within 48 hours of symptom onset. A total of 76 patients (32.07%) were diagnosed with PRES. In the PRESþ group, the neurological symptoms recorded were headache in 64 patients (84.2%), visual disturbance in 36 patients (47.4%), and seizure in 20 patients (26.3%); 31 patients (40.8%) were multiparous. In the PRESe group, headache was present in 139 patients (86.3%), visual disturbance in 42 patients (26.1%), and seizure in 11 patients (6.8%); 41 patients (25.5%) were multiparous. The factors with statistically significant differences between the PRESþ and PRESe groups were age (p¼0.017), seizure (p<0.001), visual disturbances (p¼0.002), and multiple production history (p¼0.018). The age of patients in the PRESþ group (28.24 5.88 years) was younger than the of the PRESe group (30.11 5.47 years; p¼0.017), and there was a significant difference in D-dimer levels (p<0.001) and platelet counts (p<0.001; Table 1). Blood pressure, although higher in the PRES group, had no significant correlation with the presence of PRES (Fig 1). Three factors were independently related to PRES on multilogistic regression: seizure (odds ratio [OR], 2.760; 95% confidence interval [CI]: 1.087e7.011; p¼0.033), visual disturbances (OR¼2.062 95% CI:
Table 1 Demographic, clinical, and laboratory data among posterior reversible encephalopathy syndrome negative (PRESe) and positive (PRESþ) patients.
a
Parameter
PRESe (n¼161)
PRESþ (n¼76)
p-Value
Age (years) Headache Visual disturbances Seizure Multiple production history SBP (mmHg) DBP (mmHg) MBP (mmHg) Platelet count (109/l) Haemoglobin (g/l) D-dimers (mg/l) Creatinine (mmol/l)
30.115.47 139 (86.3%) 42 (26.1%) 11 (6.83%) 41 (25.5%)
28.245.88 64 (84.2%) 36 (47.4%) 20 (26.3%) 31 (40.8%)
0.017a 0.665 0.002a 0.000a 0.018a
155.9123.97 100.8215.22 119.1617.36 171.2260.15 114.8219.06 971.671156.94 89.67318.90
161.1321.68 101.9312.66 121.7114.47 130.9562.75 112.7822.45 1758.181605.68 76.9322.67
0.108 0.580 0.267 0.000a 0.469 0.000a 0.728
Statistically significant at p<0.05. SBP, systolic blood pressure; DBP, diastolic blood pressure; MBP, mean blood pressure.
3
1.033e4.115; p¼0.004), multiple production history (OR¼3.637; 95% CI: 1.068e8.228; p¼0.002). In the comparison of pre-eclampsia and eclampsia patients, PRESþ (p¼0.000), visual disturbances (p¼0.000), seizure (p¼0.000), platelet count (p¼0.008) were statistically significant between the two groups (Table 2). PRESþ (OR¼3.217; 95% CI: 1.346e7.686; p¼0.009), visual disturbances (OR¼4.283; 95% CI: 1.843e9.953; p¼0.001) had strong association with eclampsia. Seventy-six patients were diagnosed with PRES: 20 with eclampsia and 56 with pre-eclampsia. When comparing pre-eclampsia and eclampsia, visual disturbances (p¼0.000), seizure (p¼0.000), and platelet count (p¼0.029) were different between the two groups. Age, headache, multiple production history, BP, haemoglobin, D dimers were not statistically significant (Table 3). After multilogistic regression, visual disturbances (OR¼7.200; 95% CI: 2.116e24.496; p¼0.002) had a strong association with eclampsia among PRESþ patients. A total of 30 patients (39.47%) with PRES demonstrated cytotoxic oedema (Fig 2), while 46 PRES patients had vasogenic oedema (Fig 3). Visual disturbances (p¼0.024), multiple production history (p¼0.040), and D-dimer level (p¼0.044) were statistically different between the two groups. No other parameters, including haemoglobin and platelet count, age, SBP, DBP, or MBP, or related lesions were statistically different between the two groups (Table 4). After multi-logistic regression, only the presence of visual disturbances (OR¼2.947; 95% CI: 1.135e7.648; p¼0.026) was independently associated with cytotoxic oedema. The occipital and parietal lobes were the most commonly involved regions (Fig 4). In patients with eclampsia, the parietal lobe was most commonly involved (18/20), followed by the occipital lobe (17/20); in the pre-eclampsia group, the occipital lobe was most frequently involved (45/56), followed by the parietal lobe (42/56). The BG, brain stem, and cerebellum were also frequently involved regions; BG involvement was especially common in the preeclampsia group (28/56; Fig 5); however, no statistically significant difference could be found in the location of lesions between patients with pre-eclampsia and eclampsia. All 76 patients with PRES were followed for 1 month after delivery. All patients underwent follow-up MRI and it was demonstrated that their neuroimaging manifestations were reversible.
Discussion Pre-eclampsia is one of the most serious disorders of pregnancy. Characterised by hypertension and proteinuria, it usually develops after 20 weeks of gestation.16 If one or more convulsions complicate pre-eclampsia, the patient is diagnosed with eclampsia. Pre-eclampsia or eclampsia can cause central nervous system disturbances such as subarachnoid haemorrhage, acute cerebral infarction, cerebral haemorrhage, and cerebral venous sinus thrombosis.17 All of these complications may have long-term sequelae. PRES, a common neurological complication reported in patients
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Figure 1 BP comparison between PRESe and PRESþ.
with eclampsia and pre-eclampsia, involves neurological symptoms such as headache, dizziness, nausea, vomiting, visual disturbances, convulsions, and even coma; however, patients usually have a good neurological outcome.18 Malignant and rapid onset of hypertension, eclampsia, immunosuppressive therapy, transplantation, circulating toxic mediators, sepsis, and autoimmune conditions are commonly identified as potential inducements. PRES may occur as a result of either breakdown of cerebral autoregulation or destruction of the bloodebrain barrier, leading
Table 2 Demographic, clinical, and laboratory data among pre-eclampsia and eclampsia patients.
Age (year) PRESþ Seizure Headache Visual disturbances Multiple production history SBP (mmHg) DBP (mmHg) MBP (mmHg) Platelet count (109/l) Haemoglobin (g/l) D-dimers (mg/l) Creatinine (mmol/l) a
Pre-eclampsia (n¼206)
Eclampsia (n¼31)
p-Value
29.735.58 56 (27.2%) 0 (0%) 173 (84%) 57 (27.7%) 62 (30.1%)
29.406.55 20 (64.5%) 31 (100%) 30 (96.8%) 21 (67.7%) 10 (32.3%)
0.127 0.000a 0.000a 0.059 0.000a 0.808
157.3923.97 100.7414.55 119.6216.79 162.5360.90 113.7519.34 1162.891300.89 85.42281.91
158.9018.93 104.0613.48 122.3414.21 130.2275.19 116.9225.29 1629.231699.84 86.6629.70
0.737 0.233 0.393 0.008a 0.416 0.076 0.981
Statistically significant at p<0.05. SBP, systolic blood pressure; DBP, diastolic blood pressure; MBP, mean blood pressure; PRESþ, posterior reversible encephalopathy syndrome positive.
to vasogenic oedema or endothelial dysfunction.19e23 In the present study, the correlation between pre-eclampsiaeeclampsia and PRES was studied. Although no statistical difference in BP was found, the PRESþ group did have slightly higher BP values. Although dynamic changes in the present patients could not be tested, other studies have indicated that PRES in eclamptic patients can develop without a significant rise in BP.12 “Relative hypertension” may be a crucial factor for the development of PRES.
Table 3 Demographic, clinical, and laboratory data among pre-eclampsia and eclampsia among posterior reversible encephalopathy syndrome patients.
Age (years) Headache Visual disturbances Seizure Multiple production history SBP (mmHg) DBP (mmHg) MBP (mmHg) Platelet count (109/l) Haemoglobin (g/l) D-dimers (mg/l) Creatinine (mmol/l)
Eclampsia (n¼20)
Pre-eclampsia (n¼56)
p-Value
29.406.55 17 (85%) 16 (80%) 20 (100%) 9 (45%)
27.825.63 47 (84%) 20 (35.7%) 0 (0%) 22 (39.3%)
0.306 0.910 0.000a 0.000a 0.656
156.6519.83 102.5015.16 120.5515.33 104.7970.51 111.9723.16 1683.501907.83 85.4432.27
162.7322.25 101.7311.79 122.0714.29 140.2957.56 113.0622.40 1784.861501.85 73.8917.47
0.284 0.818 0.691 0.029a 0.853 0.810 0.05
a Statistically significant at p<0.05. SBP, systolic blood pressure; DBP, diastolic blood pressure; MBP, mean blood pressure.
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Figure 2 MRI images of the brain of a 23-year-old woman with preeclampsia. (a) FLAIR MRI shows hyperintensity within the bilateral parietal lobe. (b) DWI shows restricted hyperintensity in left parietal lobe. (c) ADC image shows hyperintensity in the bilateral parietal regions but relative hypointensity in the corresponding restricted diffusion region.
In the present study, visual disturbances, seizure, and multiple production history were independent risk factors that relate to PRES. Visual disturbance as a clinical symptom included cortical blindness, blurred vision, and aethomma. Although the pathogenesis of PRES is not yet fully clarified, disturbance of the cerebral autoregulation mechanism and impairment of endothelial function has been widely accepted. In PRES cases, direct toxic effects on endothelium or vessel expansion by rising BP may comparatively weaken the effect of myogenic autoregulation. Therefore, neurogenic mechanisms take over the regulation of cerebral perfusion. In this way, posterior circulation areas become more sensitive to BP elevation owing to a relative lack of sympathetic nerves. Limits of cerebral autoregulation pass beyond the normal levels of blood pressure and vasogenic oedema occurs in the posterior circulation, especially in the occipital lobes and parietal lobes.24,25 In the present study, the occipital and parietal lobes, as visual centres, were the most commonly affected regions. This explains why visual disturbances are more common in PRES groups and are an independent risk factor for PRES. Bilateral and symmetrical vasogenic oedema or cytotoxic oedema involving the cortical and subcortical regions of the occipital and parietal lobes are most commonly seen in PRES.18,19 Similarly, seizure as a clinical symptom is thought to result from fluid in the cortex and white matter. Cerebral oedema was present in all of the present cases with
seizures. Seizure reflects fluid extravasation and oedema across the cortex, subcortex, and white matter, which is caused by cerebral hyper-perfusion pressure.22,23 In the present study, multiparity was found to be another independent risk factor with PRES. Kari et al.26 found that patients with pre-eclampsia and eclampsia experience an excessive inflammatory response: leukocyte activation, and pro-coagulant and anti-angiogenic factors together lead to vascular endothelial damage and dysfunction, which could be another pathomechanism for PRES. Multiparity together with pre-eclampsia or eclampsia may produce an excessive inflammatory response, which causes endothelium dysfunction leading to PRES. When comparing eclampsia with pre-eclampsia patients, PRES occurred in over half of the eclampsia patients (64.5%), which was much higher than pre-eclampsia patients (27.2%). Multiple regression showed that PRES was as independent related factor for eclampsia. PRES, as a result of either breakdown of cerebral autoregulation or destruction of the bloodebrain barrier, leads to vasogenic oedema or endothelial dysfunction. Cerebral oedema might induce seizure in women with pregnancy, especially cortical or subcortical oedema, which ultimately leads to the occurrence of eclampsia.27,28 Cooray et al.29 found visual symptoms can arise from different parts of the visual pathway, it occurs in approximately 25% of pre-eclamptic and 19e45% of eclamptic
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Figure 3 MRI images of the brain of a 20-year-old woman with antepartum eclampsia. (a) T2-weighted imaging shows oedema involving the bilateral occipital regions. (b) ADC and (c) DWI show involvement of the region with vasogenic oedema.
Table 4 Demographic, clinical, laboratory, and radiological data with vasogenic oedema and cytotoxic oedema among posterior reversible encephalopathy syndrome patients.
a
Parameter
Vasogenic oedema (N ¼ 46)
Cytotoxic oedema (N ¼ 30)
p-Value
Age (years) Headache Visual disturbances Seizure Multiple production history Related lesions Frontal Temporal Parietal Occipital Brainstem Cerebellum Basal ganglion SBP (mmHg) DBP (mmHg) MBP (mmHg) Platelet count (109/l) Haemoglobin B (g/l) D-dimer (mg/l)
29.206.14 46 (100%) 17 (37%) 10 (21.7%) 23 (50%)
26.775.22 30 (100%) 19 (63.3%) 10 (33.3%) 8 (26.7%)
0.078 1.000 0.024a 0.262 0.040a
21 (45.7%) 9 (19.6%) 34 (73.9%) 39 (84.8%) 4 (8.7%) 7 (15.2%) 24 (52.2%) 160.9620.25 101.9812.12 121.7013.67 122.8255.17 108.8217.76 2057.021815.57
14 (46.7%) 6 (20%) 26 (86.7%) 24 (80%) 2 (6.7%) 7 (23.3%) 15 (50%) 161.4024.06 101.8713.66 121.7315.87 143.4172.07 118.8427.40 1299.971092.68
0.931 0.963 0.183 0.588 0.748 0.372 0.853 0.931 0.970 0.991 0.163 0.057 0.044a
Statistically significant at p<0.05. SBP, systolic blood pressure; DBP, diastolic blood pressure; MBP, mean blood pressure.
women, and comprises blurry vision, diplopia, amaurosis fugax, photopsia, and homonymous haemianopsia. This concurs with the present study, as a higher incident of visual disturbance was found in eclampsia patients (67.7%) than pre-eclampsia patients (27.7%), and logistic regression analyses indicate that visual disturbance is an independent factor for eclampsia. Eclampsia patients sustain intense organ hypertransfusion and endothelial dysfunction, particularly occurring in the posterior region, as a result they are more likely to have visual disturbance. The ratio of visual disturbance among eclampsia patients (80%) is significantly higher than that of patients with preeclampsia (35.7%) among PRES patients, and multiple regression shows visual disturbance is an independent related factor for eclampsia. Combined with the discussion above, visual disturbances have a strong association with eclampsia whether patients present with PRES or not. Two major theories are proposed to clarify the pathomechanism of PRES: cytotoxic oedema theory and vasogenic oedema theory. The cytotoxic oedema theory argues that cytotoxic oedema is associated with vasoconstriction and local cerebral ischaemic necrosis. The vasogenic oedema theory supports that elevated vasogenic BP overcomes cerebral autoregulation, leading to cerebral vasodilatation and vasogenic cerebral oedema. The relation of DWI
Please cite this article in press as: Dong XY, et al., Clinical and radiological features of posterior reversible encephalopathy syndrome in patients with pre-eclampsia and eclampsia, Clinical Radiology (2017), http://dx.doi.org/10.1016/j.crad.2017.06.009
X.Y. Dong et al. / Clinical Radiology xxx (2017) 1e9
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Figure 4 T2-weighted MRI images of a 26-year-old woman with antepartum eclampsia showing involvement of bilateral BG (a) occipital and (b) parietal regions.
Figure 5 Distribution of lesions in MRI. Please cite this article in press as: Dong XY, et al., Clinical and radiological features of posterior reversible encephalopathy syndrome in patients with pre-eclampsia and eclampsia, Clinical Radiology (2017), http://dx.doi.org/10.1016/j.crad.2017.06.009
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X.Y. Dong et al. / Clinical Radiology xxx (2017) 1e9
findings to ADC can help differentiate vasogenic oedema from cytotoxic oedema.22,30 The present study concurs with previous studies of vasogenic oedema, but the cytotoxic oedema in PRES may not be the same as in cerebrovascular ischaemia. By investigating the neuroimaging of patients with PRES, some cytotoxic oedema (using DWI criteria) occurred in the centre of large areas of vasogenic oedema, i.e., occurred as transient cytotoxic oedema. As the vasogenic oedema resolves, cytotoxic oedema eases at the same time; this is not the same with cytotoxic oedema caused by acute cerebral infarction where there are long-term sequelae. In the present study, visual disturbances were more common in patients with cytotoxic oedema (63.3%) than in those with vasogenic oedema (37%), and visual disturbances were found to be independent related factors for cytotoxic oedema in PRESþ patients. This high frequency of cytotoxic oedema present in pre-eclampsia or eclampsia may be caused by endothelial damage, which is the most crucial factor for PRES in pre-eclampsia and eclampsia patients.9,17 A high level of endothelin, a potential vasoconstrictor peptide, can lead to reversible narrowing of large and medium-sized cerebral arteries, which may be responsible for vasospasm.16 Severe hypertension also promotes cerebral overregulation, vasoconstriction, infarction, and cytotoxic oedema formation.18 Posterior areas, such as visual centre, are easily influenced by endothelial damage, vasospasm, and vasoconstriction, which may impair visual pathways and lead to visual disturbances. Other possible aetiologies including: haematological malignancies,31 post-streptococcal glomerulonephritis,32 polyarteritis nodosa,33 intravenous cyclophosphamide therapy,34 and acute intermittent porphyria35 could also lead to PRES. The aetiology, pathogenesis, and prognosis of PRES are associated with the primary disease. Early diagnosis and prompt treatment of the primary disease could improve the prognosis. The present study is the largest to include both eclampsia and pre-eclampsia patients who underwent MRI for PRES evaluation; however, the present study has limitations. First, this was a single-centre, retrospective study, and selection bias may be present. Second, because of the short follow-up period (1 month), the long-term prognosis of patients with pre-eclampsia and eclampsia and PRES could not be determined. In conclusion, PRES is present in 32.07% of patients with pre-eclampsia and eclampsia at Shengjing Hospital of China Medical University. Visual disturbances, seizure, and multiparity were independent risk factors for PRES. Visual disturbances have strong association with eclampsia whether patients have PRES or not. Visual disturbances are also relevant to cytotoxic oedema among PRESþ patients. The parietal and occipital lobes are the most commonly involved regions in PRES; there is no difference in the regions involved between pre-eclampsia and eclampsia patients. PRES can be alleviated with prompt diagnosis and intensive treatment.
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Please cite this article in press as: Dong XY, et al., Clinical and radiological features of posterior reversible encephalopathy syndrome in patients with pre-eclampsia and eclampsia, Clinical Radiology (2017), http://dx.doi.org/10.1016/j.crad.2017.06.009