Chronic kidney disease (CKD) is associated with several neurological conditions. Traditional risk factors for CKD, such as diabetes and hypertension, as well as nontraditional risk factors, such as free radical injury and abnormal calcium phosphorus deposits, contribute to various neurocognitive and neurostructural diseases. In end-stage renal disease (ESRD), white matter alterations and cerebral edema have been observed, possibly due to the breakdown of the blood-brain barrier mediated by urea-activated metalloproteinase [1,2]. Dialysis in patients with ESRD has also been associated with white matter alterations and cerebral edema [3]. Patients with posterior reversible encephalopathy syndrome (PRES) improve radiologically within 5 days, followed by clinical improvement within 2 weeks after the inciting factor has been treated [4]. The radiological recovery follows clinical betterment. We present a case of malignant cerebral edema that developed within 17 hours. Despite temporary minor radiological improvements, there was no significant clinical improvement upon treatment of the inciting events, which led to her death. We highlight this atypical variant of malignant PRES and the need for aggressive management, often surgery when suspected.

We report the case of a 65-year-old female with hypertension and CKD who was brought to the emergency department showing tonic-clonic limb movements, bowel incontinence, and uprolling of the eyes, as observed by her husband at their residence, indicating a generalized tonic-clonic seizure (GTCS). There was no history of organ transplantation, intake of immunosuppressants, immunomodulators, or chemotherapeutic drugs, or administration of iodine contrast, and there was no family history of renal disease.

Upon arrival, she presented in a drowsy state with a Glasgow Coma Scale (GCS) score of 6, a pulse rate of 123 beats/min, and a blood pressure of 210/100 mm Hg. Nitroglycerin infusion was initiated to manage her hypertension. She received a loading dose of intravenous levetiracetam (2 g) followed by a maintenance dose of 500 mg three times a day to prevent further seizure episodes. A plain computed tomography (CT) brain scan was performed to rule out a hemorrhage. Blood pressure reduced to 140/90 mm Hg over 5 hours after starting nitroglycerin infusion. During observation in the intensive care unit, the patient experienced another GTCS. Consequently, lacosamide (400 mg) was administered intravenously. Interictal electroencephalogram (EEG) was performed, and generalized polyspikes were observed (Fig. 1).

In view of the poor GCS score and ongoing subclinical seizure activity, she was intubated, and a midazolam infusion was started. Once stabilized, repeat CT angiography was performed within 12 hours of the previous CT scan. Measures to reduce intracranial pressure were initiated, and a neurosurgical opinion was sought. The neurosurgical team recommended nonsurgical conservative management, including mannitol administration, hyperventilation, and hypothermia. Additionally, a nephrologist was consulted due to the presence of hyperkalemia (potassium level, 6.4 mEq/L), creatinine level, 7.01 mg/dL, and normal serum calcium and magnesium levels. Hemodialysis was initiated in response to these findings.

Repeat CT was performed. The initial CT scan showed no focal lesions, significant edema, or hemorrhage (Fig. 2A). However, after 12 hours, diffuse parenchymal edema with a midline shift was observed (Fig. 2B). Although the edema decreased after 3 days (Fig. 2C), mental status did not improve. Due to prolonged ventilation, a tracheostomy was performed. After discontinuation of the midazolam infusion, she exhibited minimal response to deep pain stimuli, with her pupils measuring 3 mm on the right with a brisk response to light and 2.5 mm on the left with a sluggish response to light. She was unable to tolerate a weaning trial (while on a pressure-regulated volume control mode of ventilation).

With no significant improvement observed, an magnetic resonance imaging (MRI) was performed to assess the prognosis of the case. The MRI revealed features of malignant PRES (Fig. 3) and Duret hemorrhages (Fig. 4), which were indicative of herniation. With no improvement observed in her clinical condition, it was decided, after discussion and after obtaining consent, not to escalate the therapy and to provide only supportive care. Eventually, she succumbed to her condition and had a cardiac arrest on day 5 of admission.

PRES is typically diagnosed based on the clinical presentation and radiological findings. It is characterized by reversible subcortical vasogenic edema and can manifest with symptoms such as altered mental status, seizures, vomiting, visual field defects, and headache. While neuroimaging commonly shows edema in the parieto-occipital region, a generalized bilateral presentation is observed in certain cases [5,6]. Additionally, PRES can occur in various contexts, including post-pregnancy and as a result of conditions such as polyarteritis nodosa [7].

Malignant PRES, which is a variant of atypical PRES, lacks specific diagnostic criteria. Akins et al. [8] defined it based on clinical features, including a GCS score of <8, clinical deterioration despite standard treatment for elevated intracranial pressure, and radiological evidence of edema or intracerebral hemorrhage causing a mass effect. This may involve effacement of basal cisterns and herniation of brain structures. Martins and Marrone [9] characterized malignant PRES by permanent neuronal damage or death, contrasting with the reversible damage observed in typical PRES. In our case, the patient presented a GCS score of 6, did not show improvement with standard management for increased intracranial pressure, and exhibited cerebral edema, herniation, and Duret hemorrhages on neuroimaging, aligning with the criteria for malignant PRES as described above.

In CKD, a diminished total nephron mass compromises the usual blood pressure autoregulation mechanism, increasing susceptibility to malignant PRES [10]. Malignant PRES may develop due to injury to the brain from status epilepticus and a hypertensive crisis in an already disrupted autoregulation, leading to fluid transudates and edema. A case study by Rodriguez et al. [11] reported a diabetic ketoacidosis episode precipitating malignant PRES with bilateral occipital and right frontal lobe edema. Another study by Hinchey et al. [12] involving 15 patients with PRES highlighted that 12 experienced sudden blood pressure elevation, with eight having kidney dysfunction. Our patient, with CKD and accelerated hypertension, had similar risk factors predisposing to malignant PRES.

Poor prognostic indicators, such as cytotoxic edema and hemorrhage, present in our case, were discussed by Martins and Marrone [9]. Our patient presented with treatment-resistant status epilepticus and accelerated hypertension and showed no neurological improvement despite standard care. Neuroimaging revealed diffuse cerebral edema with a midline shift, herniation, and hemorrhage, indicative of malignant PRES. The patient had no history of fever, disorientation, or contact with any individual with symptoms of viral infection. Although serum ADAMTS13 levels were not checked, there was no thrombocytopenia or anemia, the retic count was normal, and there was no clinically visible purpuric rash. Therefore, excluding thrombocytopenic purpura and hemolytic uremic syndrome. Antinuclear antibody, rheumatoid factor, anti-cyclic citrullinated peptide and antineutrophil cytoplasmic antibodies were negative, ruling out vasculitis. Urine porphobilinogen was negative. An autoimmune encephalitis panel test was performed, which tested negative for NMDA receptor antibody, AMPA (GluR1 & GluR2) antibody, GABA B receptor antibody, and VGKC (LGI1, ASPR2) antibodies. MRI findings were not typical of seizure-induced brain injury. Fluctuating blood pressure and renal failure were risk factors for the development of PRES in our patient.

Early suspicion of malignant PRES is crucial for prompt diagnosis as it allows for the timely initiation of aggressive intracranial pressure management and neurointensive care. Decompressive craniectomy initiated early has been associated with improved outcomes in malignant PRES [9]. This case highlights the importance of vigilant blood pressure control and proactive management of status epilepticus in high-risk patients with PRES to mitigate the risk of the malignant variant.

In conclusion, this case highlights the possibility of a devastating clinical entity of malignant PRES in hypertensive crisis in patients prone to defective blood pressure autoregulation. Early recognition and aggressive management of malignant PRES with intracranial pressure monitoring and craniectomy early in the disease may lead to favorable outcomes [8]. This is supported by our case, as even with early diagnosis and neuroimaging and EEG monitoring revealing gradual improvement, neurologists and surgeons may consider aggressive management in addition to standard care. Further research is essential to identify the underlying pathophysiology and improve the outcomes of malignant PRES.