Posterior reversible encephalopathy syndrome (PRES) is an increasingly recognized neurological disorder characterized by acute or subacute neurological manifestations including encephalopathy, seizures, headache, visual disturbances, and focal deficits typically accompanied by radiological findings of vasogenic edema, most commonly in the parieto-occipital regions[1]. Although first described as "reversible posterior leukoencephalopathy syndrome" by Hinchey et al[2], the term PRES is now preferred because lesions may extend beyond the posterior cerebral regions and involve both white and gray matter[1]. The precise pathophysiology of PRES remains incompletely understood, but two leading mechanisms are proposed[3]. Failure of autoregulation with hyperperfusion. Under acute, severe hypertension, the autoregulatory capacity of cerebral arterioles is overwhelmed. The posterior circulation, supplied by the vertebrobasilar system, is particularly vulnerable owing to its relatively sparse sympathetic innervation. Loss of autoregulation leads to hyperperfusion, endothelial disruption, and leakage of plasma and proteins into the interstitial space, manifesting radiologically as vasogenic edema[1,4]. Endothelial dysfunction with hypoperfusion. PRES may also occur in patients with modest or even normal blood pressure, implicating endothelial injury. Inflammatory cytokines, circulating toxins, sepsis, renal failure, and autoimmune disease can trigger endothelial activation, impaired blood–brain barrier integrity, and cerebral hypoperfusion. This mechanism explains PRES associated with cytotoxic agents, immunosuppressants, and systemic inflammatory states[3,4]. PRES is associated with a wide range of predisposing conditions, primarily those causing endothelial dysfunction or abrupt blood pressure changes. Approximately 80% of patients present with acute hypertension, and for most, symptoms and imaging abnormalities resolve with blood pressure lowering[4]. However, roughly 15–30% of patients are normotensive or only minimally hypertensive at symptom onset, suggesting that in some cases hypertension is a reaction to insufficient cerebral perfusion rather than the primary cause[1]. Renal failure, systemic lupus erythematosus, and thrombotic thrombocytopenic purpura frequently coexist with PRES. Nearly half of patients with PRES have an autoimmune disorder including systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, Crohn's disease, and others although direct causality is difficult to establish because many patients also take immunomodulatory agents or have concomitant hypertension[4]. PRES is also well described in the setting of eclampsia (occurring in about half of eclamptic patients), sepsis, and shock[4]. For diagnosis, MRI is far more sensitive than CT. While vasogenic edema can sometimes be seen on non contrast CT, T2 weighted sequences, particularly fluid attenuated inversion recovery (FLAIR) are significantly more sensitive for the characteristic lesions of PRES[3,4]. Lesions typically show increased signal on T2/FLAIR sequences, with increased apparent diffusion coefficient (ADC) values on diffusion weighted imaging reflecting vasogenic rather than cytotoxic edema[5]. Edema usually involves the parieto occipital regions of both hemispheres and consistently affects the subcortical white matter, with frequent cortical involvement; it is often asymmetric but almost always bilateral[1]. Three recognized patterns are the dominant parieto occipital, holohemispheric watershed, and superior frontal sulcus patterns[3]. Atypical locations like the frontal and temporal lobes, cerebellum, basal ganglia, and brainstem can be involved, usually alongside parieto occipital changes; strictly unilateral edema or isolated brainstem/cerebellar involvement should prompt suspicion for an alternative diagnosis[1,4]. Despite its name, PRES is not always fully reversible. Most patients recover with prompt diagnosis and treatment primarily blood pressure control and removal of triggering factors with resolution of imaging abnormalities in roughly two-thirds of cases. However, delayed recognition can lead to intracranial hemorrhage, infarction, and persistent neurological deficits[1,3]. We report a 66 year old woman with multiple comorbidities who presented with altered mental status and selective mutism ten days after discharge for pneumonia with sepsis. On readmission she was in hypertensive crisis with leukocytosis and encephalopathy, with imaging initially suggestive of subacute infarction; brain MRI subsequently revealed bilateral posterior hyperintensities consistent with PRES. Her course was complicated by recurrent respiratory failure requiring re-intubation, systemic inflammatory response without proven infection, and severe, treatment-resistant hypertension. Aggressive blood pressure management and supportive care led to gradual recovery, with neurological improvement by hospital day 7.

A 66 year old woman with a history of hypertension, type 2 diabetes mellitus, chronic kidney disease stage 3B, chronic diastolic heart failure, chronic obstructive pulmonary disease, rheumatoid arthritis, systemic lupus erythematosus, fibromyalgia, obesity, and hyperlipidemia was brought to the emergency department after her son noted altered mental status, weakness, lethargy, and erratic behavior. This presentation occurred ten days after a prior hospitalization for sepsis due to pneumonia. During that admission she had been febrile (101.7 °F), hypertensive (156/49 mmHg), tachycardic (108 bpm), and hypoxic. Initial labs showed blood glucose 44 mg/dL, metabolic acidosis (pH 7.25, HCO₃⁻ 16.8 mmol/L), creatinine 2.3 mg/dL, leukocytosis, and a markedly elevated BNP (16,823 pg/mL). Chest radiography revealed left lower lobe consolidation. She was initially placed on BiPAP for acute hypoxic respiratory failure but did not tolerate it and required intubation. She was treated with cefepime and vancomycin, with cautious fluid resuscitation given her heart failure. Her course was complicated by hypotension, acute kidney injury, and transaminitis, but she gradually improved, was extubated on hospital day 2, and was discharged on oral antibiotics after a six-day stay clinically stable, cognitively intact, and without focal neurological deficits. Ten days later, she returned with worsening confusion and selective mutism. In the emergency department she was in hypertensive crisis (BP >180/100 mmHg, HR 120–130 bpm), tachypneic, with a low-grade fever. Laboratory studies revealed leukocytosis (17 ×10³/µL), creatinine 1.4 mg/dL, improved but persistently abnormal liver enzymes, elevated BNP, and mildly increased troponin. A sepsis alert was initiated and empiric cefepime was started. On examination she was awake but encephalopathic, inconsistently following commands, without focal motor deficits. Head CT demonstrated subtle left parietal hypoattenuation concerning for subacute infarct, prompting a stroke alert; she was started on aspirin and a statin, and intravenous labetalol was given for blood pressure control. Chest radiography showed significant improvement compared with the prior admission, effectively excluding recurrent pneumonia. On hospital day 2, brain MRI revealed symmetric T2/FLAIR hyperintensities involving the posterior frontal convexities, bilateral parietal and occipital lobes, and left posterior temporal lobe, consistent with posterior reversible encephalopathy syndrome. Her altered mental status was attributed to acute metabolic encephalopathy in the setting of PRES, most likely secondary to uncontrolled hypertension. She subsequently developed worsening encephalopathy and hypoxia requiring re-intubation. Empiric antibiotics were continued, but infectious disease consultants concluded that her febrile episodes represented systemic inflammatory response syndrome rather than infection; blood, sputum, urine, and MRSA-screen cultures were negative, and lumbar puncture showed no infectious process. Echocardiography revealed a left ventricular ejection fraction of 40–45% with mild left ventricular hypertrophy, similar to prior studies. Renal function improved over 48 hours, and she was extubated to nasal cannula. Blood pressure control was the primary management challenge, ultimately requiring intravenous labetalol, hydralazine, topical nitroglycerin, lisinopril, metoprolol, and amlodipine, in addition to continued antiplatelet therapy. Neurologically she improved gradually: initially mute and minimally interactive, she began speaking, followed commands, and tolerated oral intake after nasogastric tube removal. By hospital day 5 she became afebrile and her white blood cell count trended downward, and by hospital day 7 she was alert, conversational, and participating in physical therapy. She reported no visual deficits but had intermittent headaches, for which Fioricet was started for symptomatic relief. An EEG showed mild diffuse background slowing suggestive of nonspecific encephalopathy, without epileptiform activity. By day 13, her mentation had improved significantly and her blood pressure was better controlled on an oral regimen. She was discharged to a skilled nursing facility with follow-up arranged with neurology, nephrology, and cardiology, and was counseled on strict antihypertensive adherence, lifestyle modification, and close outpatient follow-up. Blood Pressure Trend (systolic/diastolic, mmHg) Day Reading 1 Reading 2 1 184/115 188/110 2 176/95 207/110 3 189/94 169/99 4 200/92 172/91 5 160/80 149/71 6 155/74 155/72 7 145/73 148/77 8 157/67 153/74 9 143/86 186/89 10 164/84 168/76 11 147/85 169/94 12 142/69 138/72 White Blood Cell Count Trend (×10³/µL) Day 1 2 3 4 5 6 7 8 9 10 WBC 17.26 17.65 17.87 16.10 13.99 13.12 11.29 10.3 9.72 9.19

This case illustrates PRES arising from a convergence of well established risk factors, acute severe hypertension, recent sepsis with an ongoing systemic inflammatory response, renal dysfunction, and autoimmune disease (systemic lupus erythematosus and rheumatoid arthritis). Each of these can independently contribute to the endothelial dysfunction and blood brain barrier breakdown that underlie PRES, and their coexistence in this patient likely acted synergistically[4,3]. The mechanisms of injury from all these triggers appear to converge on the cerebrovascular endothelium, producing the vasogenic edema that defines the syndrome[4]. The patient's marked hypertension (systolic pressures persistently above 180 mmHg on presentation) is consistent with the approximately 80% of PRES patients who present with acute hypertension, and her clinical and radiological improvement with blood pressure control supports the hyperperfusion mechanism as the dominant driver in her case[4]. At the same time, her recent sepsis, systemic inflammatory response, and autoimmune disease provide plausible substrates for the endothelial-dysfunction pathway, illustrating that the two proposed mechanisms are not mutually exclusive and may operate concurrently[1]. A key diagnostic pitfall in this case was the initial interpretation of the head CT as a subacute infarct, which triggered a stroke alert. This underscores the limited sensitivity of non-contrast CT for the vasogenic edema of PRES and the superiority of MRI, particularly FLAIR sequences, in establishing the diagnosis[4]. The MRI findings of symmetric, bilateral parieto-occipital and posterior frontal T2/FLAIR hyperintensities were characteristic of PRES and correctly reoriented management away from ischemic stroke pathways[3]. Distinguishing PRES from acute ischemic stroke is clinically important, as vasogenic edema in PRES typically shows increased ADC values, in contrast to the restricted diffusion of cytotoxic edema in acute infarction[5]. The autoimmune history is particularly relevant, as nearly half of patients with PRES have an autoimmune disorder, with systemic lupus erythematosus and rheumatoid arthritis among the most frequently described associations[4]. Whether autoimmune disease is independently causal or acts through concomitant hypertension, renal involvement, or immunomodulatory therapy remains uncertain, but immune-mediated cytokine production and endothelial activation are plausible contributors to blood–brain barrier compromise[4]. Similarly, the temporal relationship to recent sepsis is notable, as infection, sepsis, and systemic inflammation are recognized triggers of PRES through endothelial injury[3]. Management of PRES is supportive and centers on prompt control of blood pressure and removal or treatment of the underlying trigger, as there is no specific therapy[6]. In this patient, treatment resistant hypertension ultimately required a multi- agent regimen, and blood pressure normalization paralleled her neurological recovery, consistent with the observation that clinical and imaging abnormalities generally resolve with hypertension treatment[4]. Her EEG showed nonspecific slowing without epileptiform activity, and no seizures occurred; EEG is nonetheless valuable in PRES for detecting nonconvulsive seizures and status epilepticus and for characterizing encephalopathy. Cerebrospinal fluid analysis, which is characteristically normal in PRES, was useful here in excluding an infectious process. Neurological recovery by hospital day 7 and functional improvement by discharge reflects the generally good prognosis of PRES when it is promptly recognized and the underlying causes are addressed[3]. Nevertheless, PRES is not uniformly reversible, and delayed recognition can result in hemorrhage, infarction, or persistent deficits[3]. This reinforces the value of early MRI and timely blood pressure control in patients with acute encephalopathy and predisposing risk factors.

PRES should be considered in any patient presenting with acute encephalopathy, seizures, headache, or visual disturbance in the setting of acute hypertension, sepsis, renal dysfunction, or autoimmune disease. This case demonstrates how multiple risk factors can converge to precipitate PRES and highlights the importance of MRI, especially FLAIR sequences in distinguishing PRES from acute ischemic stroke when CT findings are ambiguous. Prompt blood pressure control and treatment of the underlying trigger led to full neurological recovery, consistent with the generally favorable prognosis of PRES when recognized and managed early.

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