Posterior reversible encephalopathy syndrome (PRES) is a neuroradiologic diagnosis, first described in 1996, consisting of headache, seizures, altered mental status, and a spectrum of visual deficits ranging from visual neglect to cortical blindness (1). It is often related to an acute increase in arterial blood pressure, is clinically indistinguishable from hypertensive encephalopathy, and has been associated with preeclampsia, renal failure, immunosuppressive drugs, chemotherapeutic drugs, and hypercalcemia (2,3). Imaging modalities demonstrate generally symmetric hypodensities, usually of the posterior white and gray matter. Prompt treatment of hypertension or removal of the offending drug is felt to be critical in ensuring reversibility of deficits, and irreversible deficits have been reported (2,4).
A 25-yr-old G1P0 at 36 3/7 wk gestation was admitted to a local hospital with hypertension of 160/120, mental status changes, vision loss developed over the past 24 h, 3+ proteinuria, and a platelet count of 182,000. She was treated with labetalol 20 mg IV and magnesium 4 g bolus then 2 g/h and transferred shortly after admission to the University of Utah Medical Center, where she was in acute distress: agitated, delirious, and complaining of dark vision and headache.
Our patient's sister, through a translator (the patient's native language was a Mayan dialect, and she was incoherent at the time of the examination), reported that the patient had had an appendectomy performed 3 yr prior. Her only medication was prenatal vitamins, and she had no known drug allergies. The patient's sister reported no history of tobacco, alcohol, or illicit drug use.
On presentation to the University Hospital, the patient's vital signs were: arterial blood pressure 158/95, heart rate 110, and respirations 18 breaths/min. Her cardiopulmonary examination was normal. She had 2+ pedal edema, 3+ deep tendon reflexes with clonus, was flailing all four limbs spontaneously, and was unable to cooperate with an airway examination or a fundoscopic examination in her extremely agitated state. We placed a 16-g IV, made several attempts at placing an arterial line, and since imaging of her head was indicated but unable to be obtained in her current state without general anesthesia, proceeded to the operating room (OR) for a cesarean delivery, to be followed by a computed tomography (CT) scan. This sequence allowed general anesthesia to be induced and maintained initially in the relatively controlled environment of the OR, while simultaneously removing the cause of the preeclampsia.
The patient was administered oxygen, followed by a smooth rapid sequence IV anesthetic induction with etomidate and succinylcholine, easy endotracheal tube placement, and arterial line placement. In light of her unknown intracranial pathology and possibly increased intracranial pressure, anesthesia was maintained with a propofol/ remifentanil total IV anesthetic to eliminate the uncoupling of cerebral blood flow and cerebral metabolic rate seen with inhaled anesthetics. She was also hyperventilated to an end-tidal CO2 of 30 mm Hg. The patient's arterial blood pressure decreased after induction of anesthesia from 160/120 to 80/60, and after several doses of pressors and 1 L of crystalloid, stabilized at 130/75. As the intubated and sedated patient was being transferred to the CT scanner, a critical magnesium level of 5.10 mmol/L (12.4 mg/dL) was called to the OR.
CT scan demonstrated bilateral hypodensities in the occipital and posterior parietal lobes (Fig. 1). There were no abnormalities of the ventricular system and no evidence of midline shift or mass effect. The neuroradiologist made the diagnosis of PRES.
The patient was admitted to the medical intensive care unit and treated with supportive therapy with care directed by the neurology team. On postoperative day (POD) 1, she was tracheally extubated and reported that her vision had improved. She was oriented and coherent, without any recollection of the previous day events. By POD 3, her vision had returned to baseline. She was discharged to home on POD 5.
The preeclamptic parturient presenting with mental status changes and acute focal neurologic deficits suggests a broad differential diagnosis. Given the severity of the hypertension and loss of vision, intracranial hemorrhage was of greatest concern and prompted an emergent CT scan. Distinguishing between thrombotic or embolic stroke and hemorrhagic stroke is paramount when considering treatment of arterial blood pressure, and both CT and magnetic resonance imaging (MRI) may be helpful to make the diagnosis.
PRES, also called “reversible posterior leukoencephalopathy,” typically presents with symptoms of headache, visual changes, seizures, and mental status changes. Visual changes range from loss of acuity, visual neglect, or homonymous hemianopia to complete cortical blindness. PRES is associated with an acute increase in arterial blood pressure, acute renal failure, and immunosuppressive or cytotoxic drugs (such as methylprednisolone, cyclosporine, and tacrolimus). Treatment of arterial blood pressure or withdrawal of the offending drug(s) is the treatment of choice, and usually results in complete resolution of the deficits over several days to several weeks, although partial resolution has been reported and the disease can be fatal.
Radiographically, PRES manifests on CT as hypodensities of the posterior white and gray matter. Lesions are generally bilateral and parieto-occipital, but may involve temporal or frontal lobes, brainstem, or cerebellum. T2-weighted MRI shows areas of hyperintense signal and is thought to capture the images with the best quality (5), but fluid attenuated inversion recovery sequences may improve detection of cortical/subcortical areas of injury (6). Diffusion-weighted imaging may help distinguish vasogenic edema (increased apparent diffusion coefficient) from cytotoxic edema (reduced apparent diffusion coefficient, seen in acute arterial ischemic injury) (7). While our patient's intracranial pathology would likely have been better demonstrated with a T2-weighted MRI, the diagnosis was made with the CT (obtained for its utility in diagnosing intracranial hemorrhage and for the ability to rapidly obtain images in a critically ill patient), and with the rapid improvement in her clinical status, a subsequent MRI was deemed unnecessary, as clinical resolution corresponds with radiographic resolution.
The pathophysiology of PRES is most likely, and most often reported as, vasogenic edema secondary to an acute increase in arterial blood pressure, which overwhelms the autoregulatory capacity of the cerebral vasculature, causing arteriolar vasodilation and endothelial dysfunction, leading to interstitial extravasation of fluid. However, the association with cytotoxic drugs suggests a mechanism of cytotoxic edema with disruption of the blood–brain barrier. This theory posits that an acute and significant episode of hypertension causes cerebral vasoconstriction with subsequent ischemia and formation of cytotoxic edema. Diffusion-weighted MRI usually indicates vasogenic edema; furthermore, cytotoxic edema from vasospasm and edema would not be expected to completely resolve radiographically (2,5,7). Although PRES classically manifests in parieto-occipital white or gray matter, the temporal lobes, frontal lobes, brainstem, and cerebellum may be involved (2,4). The posterior circulation is thought to be more susceptible to this type of damage, because there is less sympathetic innervation of the vertebrobasilar vasculature to protect the parenchyma from rapid increases in arterial blood pressure (5,8,9).
It is reasonable to consider whether this patient's iatrogenic critical hypermagnesemia contributed to her presentation. Although hypermagnesemia may cause a variety of neurologic and cardiopulmonary effects, the more commonly reported symptoms are confusion, bradycardia, hypotension, and respiratory depression (10,11). While the hypermagnesemia was a complicating factor, it does not account for this patient's striking course.
Acute focal neurologic changes should prompt rapid investigation, including imaging of the brain. PRES, especially in the patient presenting with the typical symptoms of headache, seizures, visual deficits, and mental status changes, should be considered and treated without delay to maximize the potential for reversibility.
1. Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, Pessin MS, Lamy C, Mas J, Caplan LR. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996;334:494–500.
2. Stott VL, Hurrell MA, Anderson TJ. Reversible posterior leukoencephalopathy syndrome: a misnomer reviewed. Intern Med J 2005;35:83–90.
3. Kastrup O, Maschke M, Wanke I, Diener HC. Posterior reversible encephalopathy syndrome due to severe hypercalcemia. J Neurol 2002;249:1563–6.
4. Servillo G, Striano P, Striano S, Tortora F, Boccella P, De Robertis E, Rossano F, Briganti F, Tufano R. Posterior reversible encephalopathy syndrome (PRES) in critically ill obstetric patients. Intensive Care Med 2003;29:2323–6.
5. Vaughan CJ, Delanty N. Hypertensive emergencies. Lancet 2000;356:411–7.
6. Phal P, Molan M, Clare I. Hypertensive encephalopathy. Australas Radiol 2002;46:319–24.
7. Rangi PS, Partridge WJ, Newlands ES, Waldman AD. Posterior reversible encephalopathy syndrome: a possible late interaction between cytotoxic agents and general anesthesia. Neuroradiology 2005;47:586–90.
8. Mabie WC. Management of acute severe hypertension and encephalopathy. Clin Obstet Gynecol 1999;42:519–31.
9. Witlin AG, Friedman SA, Egerman RS, Frangieh AY, Sibai BM. Cerebrovascular disorders complicating pregnancy—beyond eclampsia. Am J Obstet Gynecol 1997;176:1139–48.
10. Schelling JR. Fatal hypermagnesemia. Clin Nephrol 2000;53: 61–5.
11. Birrer RB, Shallash AJ, Totten V. Hypermagnesemia-induced fatality following epsom salt gargles. J Emerg Med 2002;22: 185–8.