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Hubaishi, Cherifi, El Hussein, and Abuamra: Posterior reversible encephalopathy syndrome – unusual manifestation of late postpartum eclampsia

Background

Posterior reversible encephalopathy syndrome (PRES) or reversible posterior leucoencephalopathy syndrome is a rare complication of clinico-neuroradiological entities and was first described by Hinchey et al.1 in 1996. It is usually associated with serious symptoms including headache, nausea/vomiting, stupor, confusion, vision impairment, seizures and altered mental status.2,3 The pathogenesis appears to be multifactorial, resulting in cerebral oedema due to sudden changes in blood pressure. Imaging reveals white–grey matter oedema located, in most cases, in the posterior regions of the central nervous system.4,5 Its incidence is unknown and it can affect patients of any age, although in most cases patients are young to middle-aged adults.2

Although symptomology plays an important role in making a diagnosis, definitive diagnosis is based on the conjunction of symptoms with a typical pattern of neuroradiological findings. Multiple conditions are associated with PRES: pre-eclampsia, eclampsia, hypertensive encephalopathy, drug use, renal disease, an array of autoimmune disorders and the use of cytotoxic/immunosuppressive drugs.6 Pre-eclampsia and eclampsia are among the most common conditions and may occur in pregnant or puerperal patients, making the diagnosis straightforward. In contrast, late postpartum eclampsia, which occurs after 48 hours in antenatally normotensive patients, may delay the diagnosis and, therefore, treatment, resulting in severe complications.

If PRES is diagnosed early and the treatment is started promptly, the patients recover in a few weeks. If not, the patient’s condition will deteriorate and death can result. In this article we report a case of PRES that illustrates the difficulty of diagnosis, the radiological examination findings, management of the condition and follow-up of the patient.

Case presentation

We present the case of a 33-year-old woman (parity 4 + 0) who had undergone four previous caesarean sections, who came to the emergency department complaining of a severe headache that began after the delivery of her youngest child, 13 days prior to presentation.

Previous medical history:

  • gestational diabetes mellitus in her third and fourth pregnancies, well controlled on diet (using metformin only in her final pregnancy)

  • no history of pregnancy-induced hypertension in any of her pregnancies

  • four caesarean sections

  • the first and second caesarean sections were performed for failure to progress

  • elective caesarean sections for the final two pregnancies.

During her pregnancy, the patient received regular antenatal care; her blood pressure was normal throughout her pregnancy, no blood pressure recording exceeded 125/80 mmHg and urine albumin checked every visit was negative. Her blood sugar profile was also well controlled by diet (2000 calories and 1 g of metformin daily). Her routine booking investigations showed:

  • her blood group was B positive

  • haemoglobin was 8.6 g/dl; iron was 30 mg/dl (low); transferrin was 4.41 g/l (high); total iron-binding capacity was 5.60 µg/dl; negative for sickle cell disease

  • serology: negative for the hepatitis B virus and human immunodeficiency virus, VDRL was non-reactive and rubella gave a low-positive result

  • oral glucose tolerance test was 103 mg/dl when fasting,158 mg/dl 1 hour after food and 120 mg/dl 2 hours after food

  • glycated haemoglobin was 6.3%

  • renal and liver function tests were not done routinely as the patient was not known to be hypertensive.

An elective caesarean section was performed in 2015. She delivered a healthy baby girl weighing 3.03 kg and was discharged home in good condition on day 3 post operation without any complaints, and her blood pressure chart showed values within the normal range (systolic 100–120 mmHg and diastolic 60–80 mmHg) throughout.

She was readmitted on day 13 following her caesarean section with complaints of a severe headache and blurring of vision. The headache was insidious in onset and began as a vague, mild pain that gradually increased in severity to become intolerable, causing the patient to seek medical advice. The pain was described as being continuous and radiating down the spine. The patient was not suffering from neck stiffness, photophobia, nausea or vomiting. The patient attempted to alleviate the headache with analgesics, but this was unsuccessful. Her headache did not improve with a change in posture. A general examination was performed and it was concluded that the patient had no other signs.

On examination the patient was conscious, alert and oriented, but was in distress because of the pain. Her pain score was stated as 7 out of 10. She had a BMI of 44 kg/m2, and her vital signs were as follows: temperature 36°C; pulse 59 beats per minute; blood pressure 141/81 mmHg; respiratory rate 18 breaths per minute; arterial oxygen saturation 99.1%; and Glasgow Coma Scale score 15 out of 15. A full neurological examination was performed and the findings were as follows: cranial nerves were intact; the upper and lower limbs had normal power, tone, reflexes and sensation; down-going bilateral plantar reflexes; and normal fundal examination (no papilloedema). Other systemic examinations were unremarkable.

Initial investigations requested at the time of presentation at the emergency department were a full blood count (haemoglobin 9.3 mg/dl; platelets 344 × 103/µl) and urine albumin level (negative). Magnetic resonance venography (MRV) was ordered for the patient to rule out any cerebral lesion. The patient was started on 60 mg of enoxaparin once daily.

On the second day after admission, the patient complained of blurred vision. Blood pressure readings were taken and were found to be high (142/81 mmHg) and urine albumin was negative. The patient was kept under close observation while waiting for the MRV results. Six hours later the patient developed a generalized tonic–clonic seizure, which lasted 1–2 minutes and resolved spontaneously. Immediately after the seizure, her blood pressure was checked and found to be 170/100 mmHg. After regaining consciousness, the patient was disoriented and was in a state of postictal confusion. Urine albumin (a catheter specimen) was tested again using a urine test strip and was 1+ (green, approximately 30 mg/dl), hence the patient was diagnosed as having an eclamptic fit.

A retrospective review of the patient’s records showed consistently normal blood pressure readings over the previous 6 hours, rising to 170/100 mmHg at the time of convulsions. The previous readings were acceptable (range 140–150 mmHg systolic and 80–90 mmHg diastolic) and, therefore, had not been considered as serious owing to the low suspicion of pre-eclampsia. Before the seizures and because of the non-specific symptom of headache with no other associated symptoms, the opinions of an anaesthetist and a neurologist were requested. At this stage, the initial differential diagnoses were:

  1. post-spinal headache

  2. cerebral venous thrombosis.

Cerebral venous thrombosis was ruled out after reviewing the MRV results, which showed multiple T2 hyperintense areas involving the cerebellum and cerebellar hemispheres, suggesting a demyelinating aetiology; however, the possibility of ischaemia also needed to be considered. This was deemed compatible with PRES (Figure 1).

FIGURE 1

Magnetic resonance venogram showing multiple T2 hyperintense areas in the cerebellar and cerebral hemispheres, predominantly involving the white matter.

HMJ-655-fig1.jpg

A multidisciplinary team, including obstetricians, anaesthetists, intensivists and neurologists, was involved in management of the patient. She was managed as having an eclamptic fit, and anticonvulsant magnesium sulphate (MgSO4) and an antihypertensive drug (labetalol) were administered in accordance with local guidelines (4 g of MgSO4 within 30 minutes followed by 1 g per hour for 24 hours, 200 mg of labetalol twice a day).

The patient made a swift recovery and was discharged home on day 4 post seizure. She was followed up in the neurology department and recovered completely. Control magnetic resonance imaging performed 2 weeks after seizures showed resolution of the cortical and subcortical high signal intensity with persistent deep white-matter hyperintensity, suggesting partial resolution. Imaging performed 1 month later showed complete resolution.

Discussion

Posterior reversible encephalopathy syndrome is a serious condition characterized by white matter oedema and, despite its rarity, diagnosis should be considered and recognized earlier to ensure best management because of its high mortality risk. One of the risk factors of PRES is eclampsia, which occurs in approximately 1.5–10 per 10 000 deliveries in developed countries;7 late postpartum encephalopathy accounts for 5–26% of eclamptic patients.8

Our case illustrates the difficulty of early diagnosis of PRES despite the typical presentation. Diagnosis was delayed as a result of the absence of high blood pressure or proteinuria in the intrapartum and early postpartum period. According to Sibai,8 onset of eclamptic convulsions can be antepartum (38–53%), intrapartum (18–36%) or postpartum (11–44%), and recent data have shown an increase in the number of women developing eclampsia beyond 48 hours post partum but less than 4 weeks post partum;8,9 this has been acknowledged by most experts.1012 Lubrasky et al.11 and Chames et al.12 reported that 44% and 79% of their patients, respectively, developed late postpartum eclampsia that was not identified before the occurrence of convulsions, as in our case, which has been attributed to the presence of non-specific clinical and neurological symptoms.

Eclampsia should be considered in any postpartum woman who develops any of these prodromal symptoms and a prophylactic anticonvulsant should be started.13 Further indicators include convulsions, hypertension or proteinuria.

The pathogenesis of PRES is not yet clear; it is thought to be multifactorial. However, two theories dominate: (1) the hyperperfusion theory or ‘vasogenic theory’ and (2) the hypoperfusion/ischaemic theory or ‘cytotoxic theory’. The most accepted one is the vasogenic theory. This states that in normal conditions compensatory mechanisms in the central nervous system limit any sudden increase in blood pressure, preventing fluid leakage from the intravascular space to the brain interstitium – this is regulated by the sympathetic tone.14 In PRES the acute increase in blood pressure and the damage to the endothelium may lead to increased blood–brain barrier permeability and oedema in the brain interstitium.15 The reason why the posterior regions of the brain are involved is not yet well understood: it might be because the anterior circulation of the brain is better autoregulated by the sympathetic innervation than the posterior circulation.16 Wagner et al.17 reported that the patients in their study appeared to develop PRES at lower mean peak of systolic blood pressure because of the confounding effects of endothelial dysfunction in the patients with eclampsia.

Neuroimaging is the main tool used to reach the diagnosis of PRES; the abnormalities are best demonstrated with magnetic resonance imaging. The lesions are usually symmetrical and white matter can be seen in the parieto-occipital regions.6,18 Less frequently, it may also involve the frontal, temporal and cerebellar regions.1,6

If the diagnosis is recognized early, and management is appropriate, the outcome is generally good and the lesions reversible. Patients who manifest symptoms of eclampsia (e.g. high blood pressure post partum, headache, blurred vision, albumin present in urine), like our patient, should be started on treatment unless eclampsia is excluded. MgSO4 remains the best medication to control and to prevent recurrence of eclamptic convulsions. Antihypertensive medication should also be started to control blood pressure, avoiding subsequent harmful seizures.8 Sibai8 recommends a loading dose of 6 g of MgSO4 over 15–20 minutes, followed by a continuous intravenous infusion of 2 g/h continued for at least 24 hours after the final seizure. For the same reason, blood pressure should be controlled within a safe range; Sibai8 recommends antihypertensive treatment if systolic blood pressure is between 140 and 160 mmHg and diastolic blood pressure is between 90 and 110 mmHg. The management of blood pressure and convulsions is also recommended by other authors.1921 Wagner et al.17 showed that an appropriate reduction in blood pressure might prevent vasogenic to cytotoxic oedema and cerebral infarction, which result in permanent neurological deficits. Although we routinely use the term ‘reversible’, only early recognition and prompt management prevents complications such as intracerebral haemorrhage and infarction.

Learning points

Although PRES is a rare condition, early diagnosis is essential in order to start prompt treatment and prevent complications, as PRES is associated with a high risk of mortality.

  • It is important to note that blood pressures in patients with pre-eclampsia and eclampsia who develop PRES need to be lowered, to avoid irreversible damage to the central nervous system.

  • PRES should be considered in patients developing postpartum hypertension, and if suspected the patient should be closely monitored and started on medication.

  • Computerized tomography and magnetic resonance imaging are tools that can identify the lesions present in PRES.

Conclusion

Posterior reversible encephalopathy syndrome can have different causes; however, the condition is most commonly associated with pregnancy and the postpartum period. Early diagnosis and treatment prevent complications, such as epilepsy, chronic neurological sequelae and death.

References

1. 

Hinchey J, Chaves C, Appignani B, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996; 334:494–500. http://dx.doi.org/10.1056/NEJM199602223340803

2. 

Legriel S, Pico F, Azoulay E. Understanding Posterior Reversible Encephalopathy Syndrome. Annual Update in Intensive Care and Emergency Medicine 2011. Berlin, Germany: Springer, 2011. pp. 631–53. http://dx.doi.org/10.1007/978-3-642-18081-1_56

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8. 

Sibai BM. Diagnosis, prevention, and management of eclampsia. Obstet Gynecol 2005; 105:402–10. http://dx.doi.org/10.1097/01.AOG.0000152351.13671.99

9. 

Bartynski WS. Posterior reversible encephalopathy syndrome, part 2: controversies surrounding pathophysiology of vasogenic edema. Am J Neuroradiol 2008; 29:1043–9. http://dx.doi.org/10.3174/ajnr.A0929

10. 

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11. 

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14. 

Yano Y, Kario K, Fukunaga T, et al. A case of reversible posterior leukoencephalopathy syndrome caused by transient hypercoagulable state induced by infection. Hypertens Res 2005; 28:619–23. http://dx.doi.org/10.1291/hypres.28.619

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Wagner SJ, Acquah LA, Lindell EP, et al. Posterior reversible encephalopathy syndrome and eclampsia: pressing the case for more aggressive blood pressure control. Mayo Clin Proc 2011; 86:851–6. http://dx.doi.org/10.4065/mcp.2011.0090

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19. 

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20. 

Lowe SA, Brown MA, Dekker GA, et al. Guidelines for the management of hypertensive disorders of pregnancy 2008. Aust N Z J Obstet Gynaecol 2009; 49:242–6. http://dx.doi.org/10.1111/j.1479-828X.2009.01003.x

21. 

Duley L, Henderson-Smart D. Magnesium sulphate versus diazepam for eclampsia. Cochrane Database Syst Rev 2003; 4:CD000127. http://dx.doi.org/10.1002/14651858.cd000127




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