Experimental Models of Posterior Reversible Encephalopathy Syndrome: A Review From Pathophysiology to Therapeutic Targets.

Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity characterized by nonspecific symptomatology (eg, headache, visual disturbances, encephalopathy, and seizures) and classically cortical and subcortical vasogenic edema predominantly affecting the parietooccipital region. PRES etiologies are usually dichotomized into toxic PRES (eg, antineoplastic drugs, illicit drugs) and clinical condition-associated PRES (eg, acute hypertension, dysimmune disorders). Although the pathophysiology of PRES remains elusive, 2 main pathogenic hypotheses have been suggested: cerebral hyperperfusion due to acute hypertension and cerebral hypoperfusion related to endothelial dysfunction. Research into the pathogenesis of PRES has emerged through the development of animal models in the last decade. The motivation for developing a suitable PRES model is 2-fold: to fill in knowledge gaps of the pathophysiological mechanisms involved, and to open new perspectives for clinical assessment of pharmacological targets to improve therapeutic management of PRES. All current models of PRES have a hypertensive background, on which other triggers (acute hypertension, inflammatory, drug toxicity) have been added to address specific facets of PRES (eg, seizures). The initial model consisted in inducing a reduced uterine perfusion pressure that mimics preeclampsia, a leading cause of PRES. More recently, a model of stroke-prone spontaneously hypertensive rats on high-salt diet, originally developed for hypertensive small vessel disease and vascular cognitive impairment, has been studied in PRES. This review aims to discuss, depending on the research objective, the benefits and limitations of current experimental approaches and thus to define the desirable characteristics for studying the pathophysiology of PRES and developing new therapies.

Dural and Leptomeningeal Diseases: Anatomy, Causes, and Neuroimaging Findings.

Meningeal lesions can be caused by various conditions and pose diagnostic challenges. The authors review the anatomy of the meninges in the brain and spinal cord to provide a better understanding of the localization and extension of these diseases and summarize the clinical and imaging features of various conditions that cause dural and/or leptomeningeal enhancing lesions. These conditions include infectious meningitis (bacterial, tuberculous, viral, and fungal), autoimmune diseases (vasculitis, connective tissue diseases, autoimmune meningoencephalitis, Vogt-Koyanagi-Harada disease, neuro-Behçet syndrome, Susac syndrome, and sarcoidosis), primary and secondary tumors (meningioma, diffuse leptomeningeal glioneuronal tumor, melanocytic tumors, and lymphoma), tumorlike diseases (histiocytosis and immunoglobulin G4-related diseases), medication-induced diseases (immune-related adverse effects and posterior reversible encephalopathy syndrome), and other conditions (spontaneous intracranial hypotension, amyloidosis, and moyamoya disease). Although meningeal lesions may manifest with nonspecific imaging findings, correct diagnosis is important because the treatment strategy varies among these diseases. ©RSNA, 2023 Online supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article. Quiz questions for this article are available through the Online Learning Center.

Posterior reversible encephalopathy syndrome during convalescence from COVID-19.

Background and aim: With an ever-increasing population of patients recovering form severe coronavirus disease 2019 (COVID-19), recognizing long-standing and delayed neurologic manifestations is crucial. Here, we present a patient developing posterior reversible encephalopathy syndrome (PRES) in the convalescence form severe coronavirus disease 2019 (COVID-19).Case presentation: A 61-year-old woman with severe (COVID-19) confirmed by nasopharyngeal real-time reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) required invasive mechanical ventilation 24-hours after admission. During her intensive care unit stay, she developed transient acute kidney injury and septic shock. She was extubated after 22 days. On day 25, she developed generalized tonic-clonic seizures. Magnetic resonance imaging (MRI) of the brain showed bilateral subcortical lesions on the parietal and occipital lobes and multiple micro-and macro-bleeds, consistent with PRES. At this point, RT-PCR for SARS-CoV-2 in a respiratory specimen and cerebrospinal fluid was negative. She was discharged home 35 days after admission on oral levetiracetam. Control MRI five months after discharge showed bilateral focal gliosis. On follow-up, she remains seizure-free on levetiracetam.Conclusions: PRES has been observed before as a neurological manifestation of acute COVID-19; to our knowledge, this is the first PRES case occurring in a hospitalized patient already recovered from COVID-19. A persistent proinflammatory/prothrombotic state triggered by SARS-CoV-2 infection may lead to long-standing endothelial dysfunction, resulting in delayed PRES in patients recovering from COVID-19. With a rapid and exponential increase in survivors of acute COVID-19, clinicians should be aware of delayed (post-acute) neurological damage, including PRES.

Acute obstructive hydrocephalus in posterior reversible encephalopathy syndrome.

Posterior reversible encephalopathy syndrome (PRES) is an uncommon, subacute neurological disorder that presents radiologically with a pattern of bilateral parieto-occipital areas of vasogenic oedema. Conditions commonly associated with PRES include autoimmune disorders, cytotoxic drugs, metabolic abnormalities and, most frequently, hypertensive emergencies. Clinically, headache, visual disturbances, seizures and an altered level of consciousness are often reported. The outcome is favourable if the underlying cause is addressed. Posterior fossa involvement resulting in obstructive hydrocephalus is a rare presentation and may be misdiagnosed as a mass lesion or infection, leading to delayed or unnecessary treatment. We describe the clinical presentation, findings on neuroimaging and conservative management of a man with PRES resulting in severe cerebellar oedema and acute obstructive hydrocephalus. This case illustrates that awareness of atypical neuroimaging in PRES is important for the management of these patients and to avoid morbidity and mortality.

Posterior reversible encephalopathy syndrome in a child with severe multisystem inflammatory syndrome due to COVID-19. / Síndrome da encefalopatia posterior reversível em uma criança com síndrome inflamatória multissistêmica grave devido à COVID-19.

Posterior reversible encephalopathy syndrome is a rare clinical and radiological syndrome characterized by vasogenic edema of the white matter of the occipital and parietal lobes, which are usually symmetrical, resulting from a secondary manifestation of acute dysfunction of the posterior cerebrovascular system. We describe a case of posterior reversible encephalopathy syndrome secondary to SARS-CoV-2 infection in a 9-year-old boy who developed acute hypoxemic respiratory failure and required assisted mechanical ventilation. The child developed multisystem inflammatory syndrome, and he was monitored in the pediatric intensive care unit and was provided mechanical ventilation and vasoactive agents for hemodynamic support. Additionally, he developed pulmonary and extrapulmonary clinical manifestations along with neuropsychiatric manifestations that required close follow-up and were verified using brain magnetic resonance imaging for timely intervention. Currently, there are few reports of children with posterior reversible encephalopathy syndrome associated with multisystem inflammatory syndrome.

A síndrome da encefalopatia posterior reversível é uma rara síndrome clínica e radiológica caracterizada por edema vasogênico da matéria branca dos lobos occipital e parietal, que geralmente são simétricos, resultante de uma manifestação secundária de disfunção aguda do sistema cerebrovascular posterior. Descrevemos um caso de síndrome de encefalopatia posterior reversível secundária à infecção por SARS-CoV-2 em um menino de 9 anos de idade que desenvolveu insuficiência respiratória hipoxêmica aguda e necessitou de ventilação mecânica assistida. A criança desenvolveu síndrome inflamatória multissistêmica e foi monitorada na unidade de terapia intensiva pediátrica, tendo-lhe sido fornecidos ventilação mecânica e agentes vasoativos para suporte hemodinâmico. Além disso, desenvolveu manifestações clínicas pulmonares e extrapulmonares juntamente de manifestações neuropsiquiátricas que necessitavam de seguimento cuidadoso, tendo sido verificadas por ressonância magnética cerebral para intervenção oportuna. Atualmente, há poucos relatos de crianças com síndrome da encefalopatia posterior reversível associada à síndrome inflamatória multissistêmica.

Breath-Hold Diving-Related Decompression Sickness with Brain Involvement: From Neuroimaging to Pathophysiology.

Central nervous system involvement related to decompression sickness (DCS) is a very rare complication of breath-hold diving. So far, it has been postulated that repeated dives with short surface intervals represent a key factor in the development of breath-holding-related DCS. We report the case of a breath-hold diver who, after repeated immersion, developed DCS with brain involvement. After treatment in a hyperbaric chamber, there was a clinical improvement in the symptoms. Magnetic resonance imaging of the brain showed hyperintense lesions in long-time repetition sequences (FLAIR, T2WI) in the left frontal and right temporal lobes. Diffusion-weighted imaging (DWI) sequences and the apparent diffusion coefficient (ADC) map were characteristic of vasogenic edema, allowing us to exclude the ischemic nature of the process. These findings, together with the acute clinical presentation, the resolution of lesions in evolutionary radiological controls and the possible involvement of blood-brain barrier/endothelial dysfunction in DCS, could suggest a new form of posterior reversible encephalopathy syndrome (PRES)-like presentation of DCS. This would represent a novel mechanism to explain the pathophysiology of this entity. We conducted a literature review, analyzing the pathophysiological and neuroimaging characteristics of DCS in breath-hold diving based on a case of this rare disease.

Síndrome de encefalopatía posterior reversible (PRES) como forma de presentación de una amiloidosis AL / Posterior reversible encephalopathy syndrome (PRES) as a presentation of AL amyloidosis

El síndrome de encefalopatía posterior reversible (PRES) constituye una entidad clínico-radiológica relacionada con múltiples etiologías con hallazgos similares en neuroimagen. Su incidencia es desconocida y su patogenia es multifactorial, englobando fenómenos de disfunción endotelial y autorregulación del flujo cerebral, entre otros. Existe una gran variedad de condiciones asociadas, siendo las más frecuentes la hipertensión, eclampsia y la terapia inmunosupresora, junto con otros fármacos, drogas, enfermedades autoinmunes e incluso la uremia. Presentamos el caso de un síndrome de encefalopatía posterior reversible secundario a afectación renal como forma de debut de una amiloidosis AL.(AU)

Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity linked to multiple aetiologies with similar neuroimaging findings. Its incidence is unknown, and its pathogenesis is multifactorial, encompassing phenomena of endothelial dysfunction and cerebral flow autoregulation, inter alia. There is a wide variety of associated conditions, the most frequent being hypertension, eclampsia, and immunosuppressive therapy, along with other drugs, autoimmune diseases, and even uraemia. We present the case of a reversible posterior encephalopathy syndrome secondary to renal involvement as a debut form of AL amyloidosis.(AU)

[Posterior reversible encephalopathy syndrome (PRES) as a presentation of AL amyloidosis]. / Síndrome de encefalopatía posterior reversible (PRES) como forma de presentación de una amiloidosis AL.

Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity linked to multiple aetiologies with similar neuroimaging findings. Its incidence is unknown, and its pathogenesis is multifactorial, encompassing phenomena of endothelial dysfunction and cerebral flow autoregulation, inter alia. There is a wide variety of associated conditions, the most frequent being hypertension, eclampsia, and immunosuppressive therapy, along with other drugs, autoimmune diseases, and even uraemia. We present the case of a reversible posterior encephalopathy syndrome secondary to renal involvement as a debut form of AL amyloidosis.

Reversible Cerebral Vasoconstriction Syndrome and Sickle Cell Disease: A Case Report.

Reversible cerebral vasoconstriction syndrome (RCVS), is rare in the pediatric population and is characterized by severe headaches and other neurologic symptoms. We present a case of RCVS occurring concomitantly with posterior reversible encephalopathy syndrome in an 8-year-old African American child with sickle cell disease (HbSS). Imaging studies including computed tomography, magnetic resonance imaging and cerebral angiography of the brain showed acute hemorrhagic stroke and a beaded appearance of peripheral cerebral vessels. In this report, we focus on the typical features of RCVS and discuss the underlying risk factors that may increase the risk in patients with HbSS disease.

Posterior reversible encephalopathy syndrome in a patient with serotonin syndrome.

Serotonin syndrome (SS) is a drug-induced clinical syndrome, characterised by a triad of cognitive impairment, autonomic hyperactivity and neuromuscular abnormalities. Hypertension, one of the common autonomic manifestations in SS, may lead to lead to several life-threatening conditions. Herein, we report a case of SS who had posterior reversible encephalopathy syndrome (PRES) because of high blood pressure.A young male with a 5-month history of chronic tension-type headache and depression had been receiving amitriptyline and paroxetine. Increment of paroxetine led to the development of various new clinical features, fulfilling the Hunter criteria of SS. MRI brain revealed high-signal intensity lesions on T2 fluid-attenuated inversion recovery, and T2-weighted imaging in the posterior regions of the occipital, parietal, temporal and cerebellum lobes, suggestive of PRES. The patient responded to cyproheptadine. Autonomic hyperactivity, due to SS, is the most likely explanation of this association.

Clinical Presentation and Risk Factors for Poor Outcomes Among Adult Patients With Posterior Reversible Encephalopathy Syndrome: A Retrospective Cohort Study.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is an acute neurological condition with unknown global incidence, variable clinical presentation, and prognosis. OBJECTIVES: To describe a cohort of patients with PRES with a focus on brain magnetic resonance imaging (MRI) patterns and their relationship with short-term clinical outcomes. METHODS: Retrospective cohort study. The authors included patients if they were older than 15 years and had a PRES diagnosis on the basis of a positive brain MRI at any time during the in-hospital stay. RESULTS: Forty-four patients were included in the present analysis. The median age was 57 years (interquartile range, 32.0-68.5) and 70.5% were women. Hypertension (59.1%), history of transplantation (27.3%), previous chemotherapy (27.3%), chronic renal failure (38.6%), and autoimmune disease (15%) were the main comorbid conditions present. The classic triad of seizures, headache, and visual impairment was present in 18.0% of the cases. Eighty-six percent of patients were admitted to the intensive care unit, with 36.0% needing invasive life support. Brain MRI showed a dominant parieto-occipital pattern in 26 patients, whereas cytotoxic edema and bleeding were present in 27.3% and 29.6%, respectively. In-hospital mortality was 11.4%. The median modified Rankin Scale at hospital discharge was 1 (0-2.5). Risk factors associated with low modified Rankin Scale scores were: headache, visual impairment, and parieto-occipital pattern. Decreased level of consciousness and mechanical ventilation requirement were associated with greater discharge disability. CONCLUSIONS: Characteristic symptoms and signs of PRES and classic MRI patterns are associated with better clinical outcomes.

The Spectrum of MR Imaging Patterns Suggestive of Pediatric Posterior Reversible Encephalopathy Syndrome in Children With Cerebral X-Linked Adrenoleukodystrophy.

BACKGROUND AND PURPOSE: Children receiving chemotherapy, or immunosuppression have an increased risk for pediatric posterior reversible encephalopathy syndrome (pPRES); pPRES is scantly described in cerebral X-linked adrenoleukodystrophy (cALD) patients, for which hematopoietic stem cell transplantation improves outcomes. This study aimed to describe distinctive lesion patterns, distribution, and evolution of neuroimaging findings in PRES in a single-center pediatric cohort of cALD. METHODS: We retrospectively identified all clinically acquired brain MRIs of children with cALD at a tertiary care university hospital between 1995 and 2020. We reviewed clinical features, conventional MRI, and diffusion-weighted imaging findings of patients with gray matter and white matter (WM) changes suggestive of concurrent PRES-cALD. Associations between the distinctive anatomic features, distribution, and abnormal signal intensity on MRI were examined with regard to the etiology and clinical outcome. RESULTS: Our search revealed a series of eight pediatric cALD patients presenting with seizures, headache, or altered mental status with MRI findings suggestive of both PRES and cALD simultaneously. In each, the cortical-subcortical vasogenic edema on fluid-attenuated inversion recovery was consistent with pPRES, overlying the periventricular WM (PVWM) involvement typical of cALD. Of these 8 patients, the cortical-subcortical lesions on FLAIR were completely reversible on follow-up MRI in 7, but only partially reversible in 1. CONCLUSIONS: It is crucial to recognize that pPRES can occur in cALD, notably, the cortical edema and leptomeningeal enhancement can accelerate the diagnosis of superimposed pPRES, while the PVWM lesions of cALD remain following the resolution of pPRES.

COVID-19-Associated PRES-like Encephalopathy with Perivascular Gadolinium Enhancement.

We describe the case of a 63-year-old woman who developed a coronavirus disease 2019-associated acute encephalopathy with perivascular gadolinium enhancement.

Contribution of excess inflammation to a possible rat model of eclamptic reversible posterior leukoencephalopathy syndrome induced by lipopolysaccharide and pentylenetetrazol: A preliminary study.

BACKGROUND: Reversible posterior leukoencephalopathy syndrome (RPLS) is a clinical-imaging syndrome as well as a critical maternal complication. The precise pathophysiological mechanism remains controversial, mostly due to the lack of a reliable experimental animal model. Because women with eclampsia almost always present with RPLS as a complication, we hypothesize that seizures induced by preeclampsia may lead to RPLS in rats. METHODS: Pregnant Sprague-Dawley rats received pentylenetetrazol (PTZ, 40 mg/kg, intraperitoneal injection) after lipopolysaccharide (LPS, 1 µg/kg, tail vein injection) to induce eclampsia-like seizures. An anatomical view and brain water content were used to ascertain the success of the model. Moreover, blood pressure, serum biochemical indicators, serum and cerebrospinal fluid (CSF) inflammatory factors, neuroinflammation markers (Iba-1 for microglia and GFAP for astrocytes by immunofluorescence) and blood brain barrier (BBB) injury markers (VE-cadherin and ZO-1 protein by Western blotting) were measured to determine the possible mechanism. RESULTS: The rat cerebral cortex was congested and oedematous, and water contents were significantly higher following LPS and PTZ treatments. Additionally, the BP, serum and CSF inflammatory factors and neuroinflammation markers were significantly elevated, while the expression levels of VE-cadherin and ZO-1 protein were significantly decreased by LPS and PTZ treatments. CONCLUSIONS: Excess inflammation may account for the phenotypes observed in this possible eclamptic RPLS rat model induced by LPS and PTZ, providing a better understanding of mechanism of RPLS. Specifically, excess inflammation leads to BBB dysfunction and subsequently results in fluid leakage that causes lesions and increases the entrance of inflammatory factors into the brain, thus increasing the neuronal excitability that triggers seizures.

Reversible Encephalopathy Syndrome (PRES) in a COVID-19 patient.

Recently WHO has declared novel coronavirus disease 2019 (COVID-19) outbreak a pandemic. Acute respiratory syndrome seems to be the most common manifestation of COVID-19. Besides pneumonia, it has been demonstrated that SARS-CoV-2 infection affects multiple organs, including brain tissues, causing different neurological manifestations, especially acute cerebrovascular disease (ischemic and hemorrhagic stroke), impaired consciousness and skeletal muscle injury. To our knowledge, among neurological disorders associated with SARS-CoV2 infection, no Posterior Reversible Encephalopathy Syndrome (PRES) has been described yet. Herein, we report a case of a 64-year old woman with COVID19 infection who developed a PRES, and we suggest that it could be explained by the disruption of the blood brain barrier induced by the cerebrovascular endothelial dysfunction caused by SARS-CoV-2.

Guillain-Barré syndrome and posterior reversible leukoencephalopathy syndrome: a rare association.

A 69-year-old woman presented with headaches and visual disturbance in the context of marked hypertension secondary to non-compliance with antihypertensive medications. She developed seizures and hyperreflexia, and MRI brain showed changes consistent with posterior reversible encephalopathy syndrome (PRES). She was treated with antihypertensives with the resolution of symptoms. Over the following week, she developed progressive distal sensory loss, weakness and areflexia. The cerebrospinal fluid examination demonstrated albuminocytologic dissociation, and electrophysiological findings were in keeping with a diagnosis of Guillain-Barré syndrome (GBS). She was treated with intravenous immunoglobulin with gradual recovery. The co-occurrence of PRES and GBS has only been described in a handful of cases. In the majority of these, the dysautonomia of GBS leads to profound hypertension and subsequently PRES. This is a rare case of PRES preceding and possibly even triggering the onset of GBS. In this report, we review the literature and discuss the potential pathogenic mechanisms for this unusual association.

Psychiatric Morbidity and Its Prognosis in Posterior Reversible Encephalopathy Syndrome.

Posterior reversible encephalopathy syndrome (PRES) is a clinically and radiologically diagnosed disorder distinguished by subcortical vasogenic cerebral edema. To date, its presentation has been described through summarized neurological categories, such as seizures, headaches, "confusion," and "altered mental function." This retrospective case series identified all cases of clinically confirmed, radiologically diagnosed PRES resulting in treatment in a large teaching hospital from 2010 to 2019. The authors conducted a search for the term "reversible encephalopathy" in the hospital clinical radiology information system, followed by an audit of scan reports and clinical records. The most common reasons for psychiatric referral were addictions, acute psychosis, depression, suicidality, and treatment refusal. Multidisciplinary staff should consider PRES as a rare, organic differential diagnosis for acute mental state changes. Physicians should be aware of elevated rates of post-PRES psychiatric symptoms and consider whether psychiatric consultation may enhance recovery.

Neuromyelitis Optica Spectrum Disorder Complicated by Posterior Reversible Encephalopathy Syndrome as an Initial Manifestation.

A 25-year-old woman was admitted to our hospital due to tonic convulsion with severe headache after having experienced symptoms of nausea and vomiting for a month. Brain magnetic resonance imaging showed extensive symmetrical lesions in the cortical and subcortical areas of parieto-occipital lobes and basal ganglia, consistent with typical characteristics of posterior reversible encephalopathy syndrome (PRES). Furthermore, some residual lesions in the left side of dorsal medulla oblongata and central area of the cervical spinal cord along with the presence of serum anti-aquaporin-4 antibody yielded the diagnosis of neuromyelitis optica spectrum disorder (NMOSD). We herein discuss the mechanism by which PRES may occur together with NMOSD.

Cerebellar Watershed Injury in Children.

BACKGROUND AND PURPOSE: Focal signal abnormalities at the depth of the cerebellar fissures in children have recently been reported to represent a novel pattern of bottom-of-fissure dysplasia. We describe a series of patients with a similar distribution and appearance of cerebellar signal abnormality attributable to watershed injury. MATERIALS AND METHODS: Twenty-three children with MR imaging findings of focal T2 prolongation in the cerebellar gray matter and immediate subjacent white matter at the depth of the fissures were included. MR imaging examinations were qualitatively analyzed for the characteristics and distribution of signal abnormality within posterior fossa structures, the presence and distribution of volume loss, the presence of abnormal contrast enhancement, and the presence and pattern of supratentorial injury. RESULTS: T2 prolongation was observed at the depths of the cerebellar fissures bilaterally in all 23 patients, centered at the expected location of the deep cerebellar vascular borderzone. Diffusion restriction was associated with MR imaging performed during acute injury in 13/16 patients. Five of 23 patients had prior imaging, all demonstrating a normal cerebellum. The etiology of injury was hypoxic-ischemic injury in 17/23 patients, posterior reversible encephalopathy syndrome in 3/23 patients, and indeterminate in 3/23 patients. Twenty of 23 patients demonstrated an associated classic parasagittal watershed pattern of supratentorial cortical injury. Injury in the chronic phase was associated with relatively preserved gray matter volume in 8/15 patients, closely matching the published appearance of bottom-of-fissure dysplasia. CONCLUSIONS: In a series of patients with findings similar in appearance to the recently described bottom-of-fissure dysplasia, we have demonstrated a stereotyped pattern of injury attributable to cerebellar watershed injury.