Posterior Reversible Encephalopathy Syndrome (PRES) Associated With Eclampsia And HELLP Syndrome

Author Information

Kulkarni S*, Mali K**, Warke H***.
(* Junior Resident, ** Assistant Professor, *** Associate Professor, Department of Obstetrics and Gynecology, Seth G S Medical College and K E M Hospital, Mumbai, India.)
Abstract
Posterior reversible encephalopathy syndrome (PRES) is a clinico-neuroradiologic entity characterized by symptoms like headache, seizures, altered consciousness, visual disturbances and a unique radiological appearance. It is associated with acute hypertensive conditions and intake of some drugs. HELLP syndrome (hemolysis, elevated liver enzymes and low platelet count) is a condition which occurs in the third trimester of pregnancy in association with severe pre-eclampsia and is considered by some as a variant of pre eclampsia. We come across cases of both these conditions separately in our clinical practice. This case report emphasizes the importance of ruling out PRES in any case of severe pre eclampsia with neurological deficit.
Introduction
PRES is a clinico-neuroradiologic condition with unique magnetic resonance imaging(MRI) and computed tomography(CT) appearance. It is associated with acute hypertensive conditions like eclampsia, renal causes and has also been described in hypertensive encephalopathy. It also occurs as a complication of therapy with some immunosuppressants (cyclosporine, tacrolimus) and antineoplastic medications.[1] PRES is considered to be a truly reversible neurologic condition if aggressive prompt treatment is employed. However, cerebral injury may become permanent in case the treatment is delayed. HELLP syndrome is a severe condition which occurs in the third trimester of pregnancy in association with severe pre-eclampsia or immediately after delivery. We report a case of severe pre-eclampsia with HELLP syndrome detected with PRES and multidisciplinary management of the same.
Case Report
A 35 year old lady, Gravida 6, Para 2, Living 2, spontaneous abortions 3 with a history of previous lower segment cesarean section presented at 35 weeks of gestation in a disoriented state. She was referred from a local nursing home in view of eclampsia with very high blood pressure (BP) and jaundice. Pregnancy induced hypertension was diagnosed at 31 weeks and oral labetalol 100mg twice a day was started. She was a known case of hypothyroidism on oral thyroxine. She had premonitory symptoms of headache since 8 days and blurring of vision since 2 days. BP at the time of presentation at the nursing home was 230/110 mm of Hg. She was given injection labetalol 80mg intravenous infusion at 4ml/hr, injection betamethasone 12 mg intramuscularly and loading dose of injection magnesium sulphate. She had one episode of convulsion followed by hematuria and was referred to our tertiary care centre. On examination, she was disoriented, uncooperative and talking irrelevantly. BP was 160/100 mm of Hg and maintenance dose of injection magnesium sulphate was continued. Abdominal examination revealed 36 weeks uterine size and fetal heart rate of 130 beats per minute. Management was commenced in the intensive care unit. Platelet count was 80,000/ cumm, alanine aminotransferase and aspartate aminotransferase was 764 and 1629 respectively. Serological viral markers for jaundice was negative. Coagulation profile was normal barring fibrinogen degradation products and D-dimer levels which were raised. Opinion was taken from hematologist. Daily coagulation profile was monitored and advise to give fresh frozen plasma if prothrombin time >3 seconds or aPTT > 6 sec was given. In case of any active bleeding or further decrease in platelet counts to less than 50,000, transfusion of four units of random donor platelets was advised. Gastroenterology assessment was done and accordingly liver function tests were monitored daily and hepatotoxic drugs were avoided. Whole blood, platelets, fresh frozen plasma and cryoprecipitate were arranged. Ophthalmology examination revealed evidence of grade I hypertensive retinopathy in both eyes with no evidence of papilledema. Strict BP monitoring was advised. A provisional diagnosis of eclampsia in post-ictal confusional state with HELLP syndrome was made. After explaining high risk condition of the patient and obtaining a valid consent, induction of labor was done with Foley’s catheter. Injection magnesium sulphate was continued by Zuspan regimen. Bleeding per vaginum was noted after a few hours at a BP 180/110mmHg and a diagnosis of abruptio placentae was made. Fetal heart rate showed decelerations and relatives were explained about the maternal and fetal condition. In view of high risk of morbidity to the patient, relatives were not willing for a cesarean section for fetal distress. Augmentation of labor was started following an assessment after expulsion of Foley’s catheter. Labor progressed and she delivered a fresh still birth male of 1.892kg vaginally. There was no evidence of postpartum hemorrhage. She remained drowsy in the post delivery period prompting the need for neuroimaging. MRI brain was done which was suggestive of PRES with hemorrhagic foci in bilateral parieto-occipital lobes. Bilateral asymmetrical hyperintensities were seen in fronto-parietal-occipital regions, bilateral cerebellar hemispheres, white matter, pons, mid brain and bilateral basal ganglia. Neurologist advised BP monitoring and oral levetiracetam was started. Liver function tests and coagulation profile were monitored. A decreasing trend in the elevated liver enzymes was noted postdelivery. Normal vaginal delivery with aggressive hypertensive control and seizure control resulted in recovery over one week and she was discharged on the tenth day in good general condition on oral labetalol and antiepileptic medication. On follow up visits, well controlled BP was noted and gradual improvement of vision occurred over the next 3 weeks.
Discussion

PRES is considered as an entity with multifactorial etiologies, mostly associated with acute hypertension. Although more than 70% of patients with PRES are hypertensive, a significant proportion have normal or only mildly raised blood pressure.[1, 2]  Breakdown in cerebral autoregulation due to uncontrolled hypertension leads to hyperperfusion and cerebral vessel damage resulting in interstitial extravasation of proteins and fluids causing vasogenic edema. Irreversible damage is seen at mean arterial pressures above 200 mm of Hg.[3] An alternative theory is that PRES is a result of a systemic inflammatory state causing endothelial dysfunction. This is supported by the observation that PRES is usually associated with a systemic inflammatory process such as sepsis, eclampsia, transplantation and autoimmune disease. However, why some cases of PRES occur without any underlying inflammation cannot be explained. Besides preeclampsia and hypertension, PRES is associated with various conditions like renal failure, immunosuppressive therapy, post-transplantation, antineoplastic drugs and some autoimmune diseases like systemic lupus erythromatosus, systemic sclerosis, Wegener’s granulomatosis and polyarteritis nodosa.[2] Cases usually present with complaints of headaches, visual disturbances in the background of high blood pressure and a characteristic radiologic picture. Severity of clinical presentation varies from visual disturbance like blurring of vision to focal neurological deficit such as cortical blindness. Seizures could be generalized tonic clonic or status epilepticus. Rarely, severe neurological presentations leading to coma maybe seen.[2] Clinical symptoms and neuroradiological findings are typically indistinguishable among the cases of PRES regardless of the underlying cause.[4] Typical MRI findings in PRES are bilateral white-matter abnormalities in vascular watershed areas in the posterior regions of both cerebral hemispheres, affecting mostly the occipital and parietal lobes. Posterior circulation is considered more susceptible to involvement owing to the reduced amount of sympathetic innervation as compared to the anterior circulation.[2] Rapid identification and removal of trigger and aggressive management mostly results in reversal of MRI changes and improved general condition within few days to weeks. Another syndrome being increasingly identified is reversible cerebral vasoconstriction syndrome, characterised by severe thunderclap headaches with or without symptoms and segmental constriction of cerebral arteries that resolves within three months. It is supposedly due to a transient disturbance in the control of cerebrovascular tone. Stroke can occur a few days after initial imaging. Calcium channel blocker nimodipine seems to reduce thunderclap headaches within 48 hours of administration but has no proven effect on hemorrhagic and ischemic complications.[5] This has to be ruled out in cases with pre monitory symptoms of headache. HELLP syndrome is a life threatening condition that can potentially complicate pregnancy in the third trimester and is named by three main features of hemolysis, elevated liver enzymes and low platelet counts.  Pathophysiology of HELLP syndrome is not well defined and it is considered as a variant of severe preeclampsia by some. Defective placental vascular remodelling during the 16-22 weeks of pregnancy results in inadequate placental perfusion. The hypoxic placenta releases various placental factors which cause endothelial and placental dysfunction by preventing them from binding endothelial cell receptors. The result is hypertension, proteinuria and increased platelet activation and aggregation. Further decrease in platelet counts due to activation of coagulation cascade and microangiopathic hemolysis and multiorgan microvascular injury including liver necrosis contribute to the development of HELLP.[2]

Conclusion
The diagnosis of PRES is rare in cases of severe preclampsia but should be considered as a differential diagnosis in cases of eclampsia. Magnetic resonance imaging serves as an important tool in ruling out one from the other and should be made available in such cases. The coexisting complications of preclampsia like HELLP syndrome or coagulopathy can make the management difficult and the prognosis guarded. However, timely intervention and multidisciplinary management can help achieve a favourable outcome and prevent severe morbid course of recovery.

References   
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Citation

Kulkarni S, Mali K, Warke H. Posterior Reversible Encephalopathy Syndrome (PRES) Associated With Eclampsia And HELLP Syndrome. JPGO 2019. Vol. 6. No. 8. Available from:https://www.jpgo.org/2019/08/posterior-reversible-encephalopathy.html