|Year : 2014 | Volume
| Issue : 2 | Page : 59-63
Posterior reversible encephalopathy syndrome
Anjan Trikha, Ankur Sharma, Rakesh Kumar
Department of Anaesthesiology, All India Institute of Medical Sciences, New Delhi, India
|Date of Web Publication||1-Nov-2014|
Department of Anaesthesiology, All India Institute of Medical Sciences, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
Posterior reversible encephalopathy syndrome is a clinicoradiological entity characterized clinically by headache, hypertension, altered sensorium and visual disturbances. It is usually seen in the setting of toxemia of pregnancy, hypertension, severe infection or in patients receiving immunosuppressant's. The magnetic resonance imaging of the brain in such patients reveals bilateral symmetrical subcortical edema in the occipitoparietal region. The treatment is primarily supportive and involves removing the underlying cause. The condition if not identified in time may lead to irreversible damage to the brain such as hemorrhage or infarction.
Keywords: Eclampsia, hypertension, immunosuppressants, posterior reversible encephalopathy syndrome, pregnancy
|How to cite this article:|
Trikha A, Sharma A, Kumar R. Posterior reversible encephalopathy syndrome
. J Obstet Anaesth Crit Care 2014;4:59-63
| Introduction|| |
Posterior reversible encephalopathy syndrome (PRES) was first described by Hinchey et al. as a reversible syndrome of headache, altered mental functioning, seizures, and loss of vision.  This condition was usually seen in patients who had received immunosuppressive therapy had eclampsia or hypertension and autoimmune diseases. Neuroimaging in these patients revealed extensive bilateral white-matter edema predominantly in the posterior regions of the cerebral hemispheres, but also involved other cerebral areas, the brain stem, or the cerebellum. Subsequently many cases of PRES have been identified and reported from across the world. While in most cases the condition is reversible, its uncommonness and varied presentation can make it difficult to identify. Furthermore, early recognition and treatment are important to prevent neurologic sequelae. In this review, we have briefly reviewed this condition with special reference to parturient.
| Incidence|| |
Cases of PRES have been described in a wide age range starting from 2 years to up to 90 years. The exact incidence of this condition in the general population or in the various high-risk groups is not known. However, most case series have described a higher incidence in females.
| Etiology|| |
Posterior reversible encephalopathy syndrome is also known as hyperperfusion encephalopathy, brain capillary leak syndrome or reversible posterior leukoencephalopathy syndrome. It is thought to occur due to an acute rise in blood pressure that overcomes the autoregulatory capacity of the cerebral circulation. This leads to disruption of the blood-brain barrier, and vasogenic edema.  The edema is usually in the parieto-occipital lobes however may involve any part of the brain or central nervous system. It has been proposed that eclampsia also represents a form of PRES. It differs from hypertensive encephalopathy in that PRES can occur at blood pressure much lower than that required to produce hypertensive encephalopathy. , This is also true for eclampsia where the clinical features may be seen at blood pressures much lower than those at which features of hypertensive encephalopathy are produced. The development of cerebral edema and neurologic complications at normal blood pressures indicates that autoregulatory dysregulation is not mandatory, but may be more related to enhanced permeability of the blood-brain barrier.
Euser et al. in their study using an animal model found that the pregnancy promoted hydrostatic brain edema when there was an acute rise in blood pressure and also predisposes the brain to other complications. 
| Pathogenesis|| |
The exact pathogenesis of PRES is not known, however two hypothesis has been postulated.
This hypothesis is relatively more popular for the development of cerebral edema in PRES. , It proposes that a severe acute rise in blood pressure can lead to failed autoregulation, hyperperfusion and injury to the capillary bed. In humans, the lower and upper limits of auto regulation are 40-60 mmHg and 150-160 mmHg respectively.  The upper limit of autoregulation is increased in sympathetic stimulation and chronic hypertension.
In animal studies it has been shown that a severe increase in blood pressure beyond the autoregulatory limit can result in passive arteriolar dilation, pinocytotic fluid transfer, injury to the capillary bed, vasogenic edema, and vessel injury with altered arterial morphology. , Evidence from studies using technetium Tc99m-hexamethylpropyleneamine oxime single-photon emission computed tomography (CT) imaging support this hyperperfusion theory.  Even though, the hyperperfusion theory sounds simplistic and is more widely accepted, it has its own limitations. Blood pressure is not increased in all patients with PRES and even when significant hypertension is present, blood pressure does not typically reach the limits of failed autoregulation. ,, The severity of brain edema in PRES also does not correlate with the severity of hypertension. ,,
According to this theory, vasoconstriction secondary to evolving hypertension and autoregulatory compensation leads to reduced brain perfusion, ischemia, and subsequent vasogenic edema. In cases of PRES with normal blood pressure, cytotoxicity has been hypothesized to be the mechanism underlying the brain edema as seen in toxemia and sepsis.  Immune system (T-cell) activation leads to release of various proinflammatory mediators from the endothelial cells. These changes result in vascular instability with vasoconstriction and downstream hypoperfusion. Blood-brain barrier dysfunction occurs, leading to vasogenic cerebral edema. ,,
| Clinical Conditions Commonly Associated with the development of Posterior Reversible Encephalopathy Syndrome|| |
The clinical conditions associated with the development of PRES are explained below.
Toxemia of pregnancy (eclampsia and preeclampsia) and hypertension
Preeclamptic women are liable to developing PRES because of a sudden increase in blood pressure. The exact incidence is not known in such patients because magnetic resonance imaging (MRI) is not routinely done in women with preeclampsia. In literature 7-20% of patient of PRES were reported to have preeclampsia or eclampsia. Onset of PRES occurred from 28 week's gestational age to day 13 postpartum. ,, It is unpredictable whether a cause and effect relationship occurs between PRES and preeclampsia/eclampsia or if these represent separate entities with overlapping of some elements. Specifically, preeclampsia and eclampsia are diagnosed based on clinical and laboratory criteria, whereas PRES is diagnosed radiographically. Hypertension is a common condition associated with PRES apart from chemotherapy and immunosuppressant therapy.
Posterior reversible encephalopathy syndrome can occur in parturient's in whom blood pressure is normal or marginally raised during the antenatal period as suggested by two recent case reports. Chhabra and Jagtap  reported a case of PRES in a 23-year-old patient, with unremarkable antenatal period, who developed convulsions in the immediate postpartum period following elective cesarean delivery of her triplets performed under regional anesthesia. In a similar case report, Triveni et al.  described a patient of postpartum PRES, a 29-year-old primigravida of 33 weeks 3 days period of gestation who presented with ante partum hemorrhage due to marginal placenta previa and underwent uneventful cesarean section under spinal anesthesia. On the fourth postoperative day, patient developed headache and generalized tonic clonic seizures.
Immunosuppressive agents (cyclosporine A,  tacrolimus - FK 506,  and sirolimus  ) and high-dose corticosteroid therapy (dexamethasone and methylprednisolone) are associated with PRES. Different drugs have different pathogenic mechanism for the development of PRES. For example, a patient on cyclosporine develops hypertension which further leads to the development of PRES. The condition usually subsides after discontinuation of cyclosporine and control of hypertension. 
Transplant recipients are at risk for PRES, due to exposure to multiple drugs and immunosuppressants. PRES has been reported after bone marrow or stem cell transplantation and after solid organ transplantation.  Hypertension was a feature and was more severe in the kidney transplant group than in the liver transplant group. 
Cancer chemotherapy agents
Agents that are associated with PRES are: Cisplatin, gemcitabine,  oxaliplatin,  carboplatin,  cytarabine,  methotrexate,  vincristine,  bevacizumab,  sunitinib,  RAF kinase inhibitor BAY 43-9006,  rituximab (anti-CD20),  and infliximab (anti-tumor necrosis factor-α).  Combination therapy with such agents further increases the incidence of PRES.
Reported in 8-24% of cases in different reports. It is most commonly associated with Gram-positive infection.  PRES has also been reported following Escherichia coli infection. 
Posterior reversible encephalopathy syndrome had been reported in different autoimmune diseases in about 8-10% cases in different reports. It had been reported in systemic lupus erythematosus,  systemic sclerosis,  polyarteritis nodosa,  Wegener's granulomatosis,  Crohn's disease, thrombotic microangiopathy,  polyangiitis, Takayasu arteritis, and Hashimoto encephalopathy.
Other rare conditions with which cases of PRES have been reported are: Sickle cell disease, Guillain-Barré syndrome, hypomagnesaemia, hyperkalemia, tumor lysis syndrome, porphyria,  pheochromocytoma, and Cushing syndrome. 
| Clinical Features|| |
The clinical presentation of PRES may be quite variable. It includes headache, altered vision, paresis, hemianopia, nausea, and altered mentation. , PRES usually presents acutely however symptoms may at times develop over a prolonged period. About 70-80% of the patients may have moderate-to-severe hypertension. In 20-30% cases blood pressure is normal or only minimally elevated.  The correlation between the severity of hypertension and the severity of clinical or radiological features of PRES has not been documented. Presenting symptoms have varied in different reports in the literature. The first clinical series describing PRES in 1996 reported acute hypertension to be the most common clinical feature in patients with PRES.  Bartynski et al. , reported seizure activity as the most common presentation. Burnett et al.  reported impaired consciousness as the most common presentation. Impairment of consciousness ranging from lethargy to coma have been described in various studies ranging from 13% to 90% of the patients. Seizures were seen in >70% of the patients. In 3-13% cases, the presenting feature was status epilepticus. Focal neurologic signs have not been reported in most series and where reported the incidence is quite low. There are no specific symptoms that are only seen in parturients.
| Neuroimaging|| |
Magnetic resonance imaging is the investigation of choice for PRES.  It typically shows bilateral symmetrical subcortical edema in the occipitoparietal region. Other commonly seen patterns include the patchy edema in the frontal lobes or confluent vasogenic edema of the frontal, parietal and occipital lobes with sparing of the temporal lobes. Edema on MRI is usually well visualized on proton density or T2-weighted images that show high signal indicating edema. Fluid-attenuated inversion recovery images help in better visualization of cortical and subcortical edema.  Diffusion-weighted images usually do not help in the diagnosis of PRES, but may help in detecting irreversible complications of PRES such as infarction or bleeding. CT findings are either normal or nonspecific. Hypodensities in the typical topographical distribution in CT are suggestive of PRES.
| Diagnosis|| |
Diagnosis is based on the clinical features and the typical MRI findings.
| Management|| |
Generalized supportive treatment along with removal of the underlying cause form the backbone of the management. However, PRES is reversible only if treated in time, otherwise permanent neurological damage or even death may occur.
Preeclampsia-eclampsia related PRES management includes the general recommendations for treatment of pregnancy induced hypertension.  Therapeutic strategies in parturients are blood pressure regulation (with labetalol, hydralazine, sodium nitroprusside, diureticis), control of seizures (with magnesium sulfate) and anti-edema therapy (with mannitol). A progressive increase in blood pressure will lead to vasogenic and cytotoxic edema resulting in cerebral infarction and permanent neurologic deficit. The definitive treatment usually requires termination of the pregnancy. 
In case a patient requires endotracheal intubation, rapid sequence intubation should be carried out in parturients, the preferred drugs being propofol, etomidate, thiopentone, and succinylcholine.  Mechanical ventilation may be required in up to 40% of the patients.  It is important in preventing cerebral hypoxia, hypercarbia and increased intracranial pressure and the associated adverse neurological outcome. Routine management of intubated and mechanically ventilated patients is indicated.
| Complications of Posterior Reversible Encephalopathy Syndrome|| |
Cerebral infarction is the earliest sign of irreversibility in PRES. In this setting, every effort should be made to exclude reversible cerebral vasoconstriction syndrome with the help of magnetic resonance angiography or conventional angiography.
Hemorrhage may occur in the cerebral, subarachnoid or intraventricular region. It is an uncommon complication of PRES. More commonly seen in the patient with bone marrow transplantation or on anticoagulant treatment. 
Edema of the posterior part of the brain, particularly cerebellum and brainstem, may cause transtentorial cerebral herniation. 
| Conclusion|| |
Posterior reversible encephalopathy syndrome is a diagnostic challenge due to nonspecific clinical presentation and associated clinical conditions of the patient especially during pregnancy. PRES may occur even after termination of pregnancy. Pathophysiology of PRES depends upon the associated disease condition, but exact pathogenesis is not known. Early recognition of posterior encephalopathy syndrome is necessary to ensure that it stays reversible.
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