Fulminant postpartum posterior reversible encephalopathy syndrome associated with hemolysis, elevated liver enzymes, and low platelet count syndrome: A case report

Abstract

BACKGROUND

Posterior reversible encephalopathy syndrome (PRES) is a neuroradiological condition commonly associated with hypertensive disorders of pregnancy, including preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Although PRES is generally considered reversible after prompt treatment, atypical and hemorrhagic variants may rapidly progress toward irreversible neurological injury and death.

CASE SUMMARY

A 33-year-old woman at 37 weeks of gestation was admitted with severe hypertension, headache, and abdominal pain. Laboratory findings were consistent with HELLP syndrome, prompting urgent cesarean delivery. Shortly after surgery, the patient developed recurrent visual disturbances, cortical blindness, confusion, and generalized seizures. Brain magnetic resonance imaging demonstrated extensive bilateral cortico-subcortical hyperintensities involving the parieto-occipital regions, basal ganglia, posterior cingulate cortex, pons, cerebellum, and splenium of the corpus callosum, consistent with atypical PRES. The patient developed hemorrhagic transformation, diffuse cerebral edema and then brain death, despite the early intensive treatment by magnesium sulfate, antihypertensive therapy, mechanical ventilation, antiepileptic treatment, osmotherapy and platelet transfusion.

CONCLUSION

Hemorrhagic central PRES associated with HELLP syndrome may rapidly evolve toward fatal neurological injury despite early diagnosis and treatment.

Key Words: Posterior reversible encephalopathy syndrome; Hemolysis, elevated liver enzymes, and low platelet count syndrome; Eclampsia; Intracranial hemorrhage; Cortical blindness; Neurocritical care; Brain edema; Case report

Core Tip: This report describes a rare and catastrophic postpartum case of posterior reversible encephalopathy syndrome (PRES) associated with hemolysis, elevated liver enzymes, and low platelet count syndrome and eclampsia complicated by hemorrhagic transformation, diffuse cerebral edema, and brain death. The case highlights that PRES is not invariably reversible and emphasizes the prognostic role of atypical magnetic resonance imaging findings, intracranial hemorrhage, and severe endothelial dysfunction.

INTRODUCTION

Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological syndrome characterized by altered mental status, seizures, headache, visual disturbances, and vasogenic edema, typically affecting the posterior brain regions, but not exclusively. Preeclampsia and eclampsia, along with dysregulation of blood pressure during pregnancy, represent significant risk factors for PRES. Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is a serious pregnancy-related disorder characterized by hemolysis, elevated liver enzymes, and thrombocytopenia, often associated with endothelial dysfunction and neurological complications. Although PRES is usually considered a reversible condition, there are still gaps in its pathophysiology, considering that severe and rarer variants accompanied by hemorrhage and diffuse cerebral edema can cause permanent neurological damage or even exitus. We report a fulminant postpartum case of atypical hemorrhagic PRES associated with HELLP syndrome and eclampsia.

CASE PRESENTATION

Chief complaints

A 33-year-old woman at 37 weeks of gestation presented with severe headache, abdominal pain, and elevated blood pressure.

History of present illness

The patient presented to the emergency department of a level I hospital with severe headache, abdominal pain, and markedly elevated blood pressure on physical examination. An emergency cesarean section was therefore performed. The newborn had Apgar scores of 9 and 9 at 1 minute and 5 minutes, respectively. Immediately after delivery, the patient developed bilateral visual disturbances followed by confusion and transient cortical blindness lasting approximately 40 minutes. One hour later, the visual symptoms recurred and progressed toward complete cortical blindness. During transfer to a tertiary referral center, the patient experienced three brief episodes of impaired awareness, followed by a generalized tonic-clonic seizure that was treated with intravenous diazepam 10 mg and levetiracetam 1 g.

Upon admission to the intensive care unit, neurological examination revealed a Glasgow Coma Scale score of 8 (E2V2M4), severe hypertension (180/100 mmHg), absent airway protective reflexes, and progressive neurological impairment requiring endotracheal intubation after administration of analgosedation and neuromuscular blockade.

History of past illness

The patient’s medical personal history was unremarkable, with one previous uncomplicated spontaneous vaginal delivery and no history of chronic hypertension, renal disease, or neurological disorders.

Personal and family history

No significant family history was reported.

Physical examination

Immediately after ceasarean delivery, the patient developed bilateral visual disturbances followed by confusion and transient cortical blindness lasting approximately 40 minutes. One hour later, visual symptoms recurred and progressed toward complete cortical blindness.

During transfer to a tertiary referral center, the patient experienced three brief episodes of impaired awareness followed by a generalized tonic-clonic seizure. Upon admission to the intensive care unit, neurological examination revealed a Glasgow Coma Scale score of 8 (E2V2M4), severe hypertension (180/100 mmHg), absent airway protective reflexes, and progressive neurological impairment requiring analgo-sedation, tracheal intubation and mechanical ventilation.

Laboratory examinations

Initial laboratory findings were consistent with HELLP syndrome[1] and included a platelet count of 67000/µL (normal range: 150000-400000 µL), hemoglobin at 11.3 g/dL (normal range: 12-16 g/dL), aspartate aminotransferase at 323 U/L (normal range: 0-32 U/L), alanine aminotransferase at 246 U/L (normal range: 0-33 U/L), alkaline phosphatase at 137 U/L (normal range: 35-105 U/L), creatinine at 0.59 mg/dL (normal range: 0.5-1 mg/dL), creatine kinase at 160 U/L (normal range: 0-170 U/L), antithrombin III activity of 68% (normal range: 75%-125%), and an international normalized ratio of 0.93 (normal range: 0.8-1.2), lactate dehydrogenase 1004 U/L (normal range 120-220 U/L), total bilirubin 2.06 mg/dL (normal range 0.2-1.2 mg/dL). Haptoglobin and peripheral smear findings were not available.

Postpartum laboratory evaluation demonstrated worsening thrombocytopenia with platelet count decreasing to 32000/μL, persistent thrombocytopenia ranging between 40000/μL and 60000/μL during the following days, and hemoglobin values ranging from 7.8 g/dL to 8.9 g/dL. Twenty-four hours after cesarean delivery, laboratory tests showed aspartate aminotransferase 482 U/L, alanine aminotransferase 215 U/L, lactate dehydrogenase 1804 U/L, creatine kinase 406 U/L, and total bilirubin 3.06 mg/dL. Laboratory abnormalities progressively improved within 48 hours.

No genetic tests were performed because of the acute clinical course and limited survival time following disease onset.

Imaging examinations

An urgent head computed tomography (CT) performed shortly after the onset of neurological symptoms demonstrated a suspected ischemic lesion involving the left nucleocapsular region.

FINAL DIAGNOSIS

Brain magnetic resonance imaging (MRI; Figure 1) performed immediately after intensive care unit admission demonstrated extensive bilateral cortico-subcortical FLAIR hyperintensities involving the parieto-occipital regions, basal ganglia, posterior cingulate cortex, cerebellum, pons, left frontal region, and splenium of the corpus callosum, findings compatible with atypical PRES and diffuse vasogenic edema, and excluding an ischemic process[2,3]. The following day, the patient initially showed transient hemodynamic stabilization with blood pressure of 140/80 mmHg, preserved urine output, reactive pupils, and normal oxygen saturation. An electroencephalogram was performed under analgesia to rule out underlying seizure activity.

Figure 1 Axial fluid-attenuated inversion recovery magnetic resonance images. A: Symmetric extensive bilateral cortico-subcortical hyperintensities involving the parieto-occipital regions within the posterior circulation territories; B: Extension of hyperintense lesions into deep central structures, including the basal ganglia and periventricular white matter; C: Diffuse bilateral vasogenic edema with widespread cortical-subcortical hyperintensities involving both posterior and central brain regions.

Within a few hours, the patient developed sudden neurological deterioration associated with bilateral areflexic mydriasis and peak hypertension (170/100 mmHg). An emergency head CT scan (Figure 2) revealed a right nucleocapsular hemorrhage with tetraventricular involvement, ventricular dilation, diffuse cerebral edema, progressive loss of gray-white matter differentiation, brainstem compression, and herniation of the cerebellar tonsils. The final diagnosis was fulminant postpartum PRES associated with HELLP syndrome and eclampsia, complicated by intracranial hemorrhage, diffuse cerebral edema and refractory intracranial hypertension, excluding other possible causes by diagnostical imaging.

Figure 2 Cranial computed tomography images. A: Massive intraventricular hemorrhage involving the lateral and third ventricles, associated with diffuse cerebral edema and ventricular enlargement; B: Blood extension into the fourth ventricle at the level of the posterior fossa, with marked brainstem compression and obliteration of the basal cisterns, findings consistent with severe intracranial hypertension; C: Right capsuloganglionic intraparenchymal hemorrhage with massive intraventricular extension, surrounding edema, hydrocephalus, and significant mass effect.

TREATMENT

The patient was treated with invasive mechanical ventilation by tracheal intubation, intravenous antihypertensive therapy (urapidil: 5 mg/hour and labetalol: 150 mg/hour) and magnesium sulfate infusion (40 g/die) to get target pressure 140/80 mmHg, levetiracetam 1000 mg twice daily, diazepam, osmotherapy with 20% mannitol 1 g/kg, oxytocin infusion, platelet transfusion. A neurosurgical consultation was requested, but an external ventricular derivation was not indicated due to thrombocytopenia.

OUTCOME AND FOLLOW-UP

Despite careful neurocritical management, the patient's neurological condition progressively deteriorated. Discontinuation of sedation revealed a deep coma with a Glasgow Coma Scale score of 3, bilateral fixed mydriasis, absent spontaneous breathing, and loss of cranial nerve reflexes. Subsequent cerebral CT angiography confirmed the absence of blood flow, and brain death was declared according to institutional protocols. During organ donor evaluation, echocardiography showed preserved cardiac function. Histopathological examination performed during organ procurement revealed mild portal fibrosis with minimal hepatic steatosis and preserved renal cortical parenchyma. The heart, liver, lungs, kidneys, and corneas were successfully allocated for organ donation.

DISCUSSION

PRES is increasingly recognized as a severe neurological complication of hypertensive disorders of pregnancy[4-6]. Although PRES is usually considered a reversible condition, severe and rare variants accompanied by hemorrhage and diffuse cerebral edema can cause permanent neurological damage or even exitus. Two main pathophysiological theories have been addressed. The first concerns impaired cerebral autoregulation of blood pressure. During pregnancy, severe hypertension can exceed the autoregulatory capacity of cerebral vessels, particularly in the posterior circulation, where sympathetic innervation appears to be less developed. This mechanism may lead to endothelial dysfunction and vasogenic edema. The second theory emphasizes endothelial dysfunction as the primary pathogenetic mechanism. According to this hypothesis, endogenous and exogenous inflammatory mediators lead to damage to the blood-brain barrier, alterations in vascular permeability, and consequent fluid extravasation into the brain parenchyma, resulting in edema.

In both HELLP syndrome and eclampsia, diffuse endothelial activation, microangiopathy, platelet consumption, and inflammatory dysregulation may contribute significantly and synergistically to the development of PRES. This case report demonstrated a number of predictive factors for an adverse neurologic outcome, including altered mental status, extensive central nervous system involvement, intracranial hemorrhage, diffuse cerebral edema, severe thrombocytopenia, and rapid postpartum progression. MRI findings showed atypical involvement of the deep gray matter and brainstem, features increasingly associated with malignant variants of PRES.

Hemorrhagic transformation is a rare but devastating complication of PRES. Cerebral hemorrhage can occur in 17% of the cases, secondary to severe hypertension, endothelial damage, coagulation abnormalities, and vascular fragility[7-10]. In our patient, rapid progression to refractory intracranial hypertension and brain death occurred despite early intensive multidisciplinary management.

Visual symptoms were the first neurological manifestation. Cortical blindness is a recognized presentation of PRES and eclampsia-related encephalopathy. However, recurrent visual disturbances associated with progressive deterioration in consciousness should immediately raise suspicion of malignant PRES, which requires urgent neuroimaging and close monitoring.

Even if there are important limitations in this case report, such as incomplete information from the initial hospital course, lack of direct intracranial pressure monitoring, and the inability to establish causality from a single case, it suggests that PRES should not always be considered a benign or completely reversible condition. Early MRI, aggressive blood pressure control, seizure management, and multidisciplinary neurocritical care are essential, particularly in postpartum patients presenting with neurological deterioration or atypical imaging findings.

CONCLUSION

Atypical hemorrhagic PRES associated with HELLP syndrome may rapidly progress toward catastrophic neurological injury despite prompt treatment. In some cases, even early recognition of malignant PRES variants and multidisciplinary neurocritical care management cannot improve maternal outcomes.