We describe a confluent deep white matter abnormalities variant of PRES, further strengthening the notion that PRES is a disorder of radiological heterogeneity. We present 2 cases of PRES with findings of diffuse but reversible vasogenic edema located in the deep periventricular white matter regions of bilateral hemispheres without a clearly posterior distribution. We feel that this represents a rare variant of PRES on imaging, thus adding to the existing radiological spectrum for this entity. Both of our patients presented with malignant hypertension (mean arterial blood pressure of 200 mmHg) and developed neurological symptoms that included encephalopathy, seizure, headache, and vision changes. Additionally, both patients presented with significant subcortical white matter edema that improved dramatically on follow-up imaging. The clinical and radiological improvement in both patients occurred following successful blood pressure management. It is possible that the deep white matter changes of PRES are seen exclusively in the setting of severe accelerated hypertension. Our case reports reveal that, in patients with hypertensive encephalopathy, a deep white matter pattern of diffuse signal changes may not necessarily indicate chronic ischemic changes and follow-up imaging studies are essential to rule out a diagnosis of PRES.
The clinical manifestations of posterior reversible encephalopathy syndrome (PRES) include encephalopathy, headache, visual disturbance, and seizure. In most cases, symptoms present acutely in the setting of accelerated hypertension, toxemia of pregnancy, autoimmune disorder, immunosuppressive treatment, or cancer chemotherapy. One essential feature of PRES is the presence of reversible subcortical vasogenic edema that has a predominantly posterior distribution on brain imaging [
Initially found unresponsive, this 49-year-old hypertensive, hepatitis-C-positive Caucasian man presented to our emergency department with witnessed clonic tonic seizures and postictal confusion. He was treated with midazolam and fosphenytoin, followed by intubation for airway protection. Three months earlier, he presented to our hospital in a hypertensive emergency that resolved upon treatment. Home medications included aspirin, amlodipine, hydrochlorothiazide, and labetalol, but he was noncompliant.
At presentation, the patient was afebrile with an initial blood pressure of 264/168 mmHg. On evaluation he was intubated and sedated. He demonstrated minimal responses to verbal and tactile stimulation. Pupils were equal and reactive to light. Corneal and gag reflexes were intact. The serum white blood cell count (WBC) was 17,100/
Magnetic resonance imaging (MRI) of the brain revealed confluent areas of abnormal T2 signals in the deep periventricular white matter regions extending into the subcortical areas and relatively sparing the corpus callosum. Patchy high T2 signals were also seen in the pons, cerebellum, thalamus, and basal ganglia. Small areas of restricted diffusion were detected in the left greater than right medial parietal and bilateral frontal lobes, with apparent diffusion coefficient (ADC) correlation (Figure
MRI findings at initial presentation (upper row) and follow-up (lower row). (a)-(b) Axial FLAIR images, taken at the levels of the hippocampi, mid lateral ventricles, and centrum semiovale, demonstrate confluent areas of abnormal high signal in the deep white matter with sparing of the subcortical white matter and overlying cortex. (d)-(e) Axial FLAIR images, at similar levels to (a)-(b), demonstrate marked decrease in the abnormal signal in the cerebral white matter. (c) shows small areas of restricted diffusion in the left greater than right medial parietal and bilateral frontal lobes, with apparent diffusion coefficient (ADC) correlation (f).
The patient’s blood pressure was controlled with amlodipine, hydrochlorothiazide, candesartan, and labetalol; his mental status significantly improved and he was extubated the following day. Following 5 days of hospitalization, he was discharged in a stable condition. Antiepileptic therapy was discontinued at discharge. A repeat MRI after 18 months showed areas of encephalomalacia in the medial parietal and bilateral frontal lobes, which most likely represents chronic infarctions. The previously noted hyperintense T2 signals in the deep white matter, cerebellum, and pons significantly improved while small areas of hyperintense signal changes were still observed in the bilateral parieto-occipital regions (Figure
This 50-year-old man presented with headache, dizziness, blurred vision, shortness of breath, and leg edema. He was admitted with a diagnosis of acute renal failure. He had a long-standing history of hypertension for 20 years without treatment. He denied smoking, alcohol drinking, or use of recreational drugs. At initial presentation, he was afebrile with a blood pressure of 240/180 mmHg. He was awake and oriented to person, time, and place but had difficulties in recalling names, spelling words backwards, and following complex commands. Cranial nerve examination was normal. Motor strength examination revealed no focal weakness. The serum WBC was 13,000/
Magnetic resonance imaging findings in case 2 at initial presentation (upper row) and follow-up (lower row). (a)–(c) Axial FLAIR images, taken at the levels of the hippocampi, mid lateral ventricles, and centrum semiovale, demonstrate confluent areas of abnormal high signal in the deep white matter with sparing of the subcortical white matter and overlying cortex. (d)–(f) Axial FLAIR images, at similar levels to (a)–(c), demonstrate marked decrease in the abnormal signal in the cerebral white matter.
The patient’s blood pressure was controlled with losartan, nifedipine, and metoprolol. His symptoms including cognitive impairment significantly improved following blood pressure reduction. He was discharged home after 1 week of hospitalization. Five months later, a follow-up MRI showed a marked reduction of the signal abnormalities previously seen in the deep white matter region (Figure
Posterior reversible encephalopathy syndrome is more frequently recognized with the increased availability of advanced MRI techniques. The underlying mechanism for PRES is felt to be an impairment of cerebral autoregulation and a breakdown of the blood brain barrier, likely triggered by mechanical stretching injuries from severe hypertension or chemical effects of various mediators such as cytokines from infections, toxins, or chemotherapy agents. The breakdown of blood brain barrier leads to an extravasation of fluid, protein, and other macromolecules, which may contribute to the formation of vasogenic edema. Differences in the cytoarchitecture and cerebral adrenergic innervation make the posterior circulation most susceptible to this process. Other superimposed mechanisms include vessel microdissection, arterial vasospasm, and microvascular thrombosis, consequently leading to superimposed parenchymal ischemia or hemorrhage [
A diagnosis of PRES is based on the following essential findings: (1) the presence of significant hypertension or other typical triggering factors such as cancer treatment or toxemia of pregnancy; (2) the occurrence of at least 1 of the following neurological symptoms: headache, seizure, visual disturbance, and mental status change; (3) the image findings of reversible predominantly subcortical vasogenic edema [
The classic MRI findings of PRES include bilateral symmetrical hyperintensities on fluid attenuated inversion recovery (FLAIR) sequence in the parieto-occipital and posterior frontal regions, with the involvement of more subcortical white matter than cortical gray matter. Such a classical pattern is typically seen in approximately 70% of patients [
We describe a confluent deep white matter abnormalities variant of PRES, further strengthening the notion that PRES is a disorder of radiological heterogeneity. Other atypical imaging findings in PRES include areas of ischemia manifesting as restricted diffusion on diffusion-weighted imaging with a correlation of decreased signal on apparent diffusion coefficient, reported in as many as 24% of patients [
The underlying mechanism for the classical posterior dominance pattern is felt to be the paucity of sympathetic innervation in the posterior brain regions, especially in the territory of basilar artery and its branches, in comparison to the carotid and anterior cerebral territories. Normally, sympathetic activation leads to arteriolar constriction in responding to severe hypertension. A relative lack of sympathetic innervation renders the posterior regions to an increased risk of hydrostatic cerebral vasogenic edema during hypertensive crisis [
It is worth noting that different imaging patterns of PRES were observed in specific clinical settings. For instance, brainstem involvement in PRES has been reported mainly in patients with malignant hypertension [
The authors declare that there is no conflict of interests regarding the publication of this paper or funding information to disclose.
The authors gratefully thank Kathleen Moser and Jacqueline Grove (medical editors, Lehigh Valley Health Network) for assistance with editing and paper preparation. This work was completed while Yuebing Li was at Lehigh Valley Health Network, Allentown, PA, USA.