Non-neurological Conditions Research Articles

Nonamyloidogenic TTR gene variants c.76G>A and c.337-18G>C are not associated with idiopathic small-fiber neuropathy.

Small-fiber neuropathy (SFN) affects only unmyelinated and thin myelinated fibers. It may be caused by amyloidogenic mutations of the transthyretin (TTR) gene, but not all TTR gene variants are pathogenic. The nonamyloidogenic c.76G>A (rs1800458) and c.337-18G>C (rs36204272) variants of TTR were recently reported to be associated with SFN. We investigated this putative association by analyzing TTR gene sequencing data retrospectively for two cohorts of patients, one with SFN and a control group. In this retrospective single-center study, we analyzed the frequency of the c.76G>A and c.337-18G>C TTR gene variants in a cohort of patients meeting a strict definition of SFN, with or without dysautonomia, a control cohort of patients investigated for nonneurological conditions, and the gnomAD international database. We included 55 SFN patients in this study, 17 of whom had dysautonomia. The allelic frequencies of the two variants in our cohort of 55 SFN patients were 7.27% for c.76G>A TTR and 5.25% for c.337-18G>C. The frequencies of both variants were statistically similar in the 337 control patients and the gnomAD database. The c.76G>A and c.337-18G>C TTR gene variants are not associated with SFN.

When the diagnosis is in the patient's hand and in the neurologist's eye.

The objective of this study was to encompass current knowledge about pathophysiological mechanisms of those specific hand postures or deformities caused by central nervous system disorders. In the era of high-resolution neuroimaging and molecular biology, clinicians are progressively losing confidence with neurological examination. Careful hand observation is of key importance in order to differentiate neurological from non-neurological conditions, central from peripheral aetiologies, and organic from functional disorders. Localizing the potential anatomical site is essential to properly conduct subsequent exams. We provided a practical guide for clinicians to recognize hand patterns caused by central nervous system disorders, avoiding mimicking conditions, thus optimizing and prompting the diagnostic pathway.

Recurrent Intensive Care Episodes and Mortality Among Children With Severe Neurologic Impairment

Children requiring care in a pediatric intensive care unit (PICU) are known to have increased risk of subsequent mortality. Children with severe neurologic impairment (SNI)-who carry neurologic or genetic diagnoses with functional impairments and medical complexity-are frequently admitted to PICUs. Although recurrent PICU critical illness episodes (PICU-CIEs) are assumed to indicate a poor prognosis, the association between recurrent PICU-CIEs and mortality in this patient population is poorly understood. To assess the association between number of recent PICU-CIEs and survival among children with severe neurologic impairment. This population-based retrospective cohort study used health administrative data from April 1, 2002, to March 31, 2020, on 4774 children born between 2002 and 2019 with an SNI diagnosis code in an Ontario, Canada, hospital record before 16 years of age and a first PICU-CIE from 2002 to 2019. Data were analyzed from November 2021 to June 2023. Pediatric intensive care unit critical illness episodes (excluding brief postoperative PICU admissions). One-year survival conditioned on the number and severity (length of stay >15 days or use of invasive mechanical ventilation) of PICU-CIEs in the preceding year. In Ontario, 4774 children with SNI (mean [SD] age, 2.1 [3.6] months; 2636 [55.2%] <1 year of age; 2613 boys [54.7%]) were discharged alive between 2002 and 2019 after their first PICU-CIE. Ten-year survival after the initial episode was 81% (95% CI, 79%-82%) for children younger than 1 year of age and 84% (95% CI, 82%-86%) for children 1 year of age or older; the age-stratified curves converged by 15 years after the initial episode at 79% survival (95% CI, 78%-81% for children <1 year and 95% CI, 75%-84% for children ≥1 year). Adjusted for age category and demographic factors, the presence of nonneurologic complex chronic conditions (adjusted hazard ratio [AHR], 1.70 [95% CI, 1.43-2.02]) and medical technology assistance (AHR, 2.32 [95% CI, 1.92-2.81]) were associated with increased mortality. Conditional 1-year mortality was less than 20% regardless of number or severity of recent PICU-CIEs. Among children with high-risk PICU-CIEs, 1-year conditional survival decreased from 90% (95% CI, 89%-91%) after the first PICU-CIE to 81% (95% CI, 77%-86%) after the fourth PICU-CIE. This cohort study of children with SNI demonstrated a modest dose-dependent association between PICU-CIEs and short-term mortality. These data did not support the conventional wisdom that recurrent PICU admissions are associated with subsequent high mortality risk.

Chapter 6 - Clinical/surgical considerations

While there are a diverse number of indications for the potential use of cell and gene therapies in people, many of the medical conditions being treated need to consider some general clinical and surgical issues, not only in designing clinical trials, but also in the eventual application of the therapy if shown to be successful. Such issues include the precision of the diagnosis and stage of disease, the presence of significant comorbidity, as well as the challenges that may be encountered in trial designs involving the neurosurgical delivery of these advanced interventions. This chapter discusses details of these issues that have arisen particularly in the field of Parkinson disease and other forms of neurodegeneration, although the general principles and considerations discussed may be equally relevant to other neurologic and nonneurologic conditions.

Unmet needs to admission in physical and rehabilitation inpatient department in Low and Middle Income Countries in 2023.

Determining the needs to access to rehabilitation structures is essential for developing effective improvement strategies. The objective of this study was to determine the percentage of unmet needs to admission to rehabilitation and their associated factors. It is a cross sectional study in the inpatient rehabilitation department Sahloul Hospital of Sousse, tertiary care center including all requests to admission. Patient demographics, diagnoses, admission decisions, and post-decision outcomes were collected for each request. Of 329 admission requests, 316 were eligible. The mean patient age was 45 years, with a male-to-female ratio of 0.84. Most requests originated from the hospital's outpatient department, neurology, and orthopedics. Among all requests, 40.5% were not admitted. Non-neurological diagnoses and patient residency were associated with non-admission. Patients with non-neurological conditions and those residing outside the city had twice the risk of non-admission. At one month, 63% of non-admitted patients experienced functional decline, and 18% were lost to follow-up. Unmet needs to admission in rehabilitation structures is high due to lack of beds. This is leading of inequity of access to such important phase of care more. This study highlighted throwing the example of physical and rehabilitation department the gap of needs and the capacity of inpatient rehabilitation facilities. Healthcare policies should prioritize increasing rehabilitation bed availability in all regions of the country.

Knowledge, attitudes and practices of the Saudi population toward people with epilepsy: narrow or wide?

BackgroundAlthough epilepsy has been acknowledged as an illness since ancient time, the public attitude toward epilepsy has not changed drastically due to the lack of appropriate information. This study aims to determine the public perceptions of epilepsy in five main regions of Saudi Arabia.MethodsIn this cross-sectional questionnaire-based study, Saudi citizens living in the major cities of the five main regions of the Kingdom of Saudi Arabia (the central, eastern, western, northern, and southern regions) completed the survey that included 27 questions about epilepsy awareness.ResultsA total of 7118 individuals from five regions participated in the survey: 6749 (94.8%) of respondents were Saudi, and 369 (5.2%) were non-Saudi. Of the 7118 respondents, 6897 respondents (96.9%) did not have epilepsy, and 3378 respondents (47.5%) stated that they had never witnessed an epileptic episode. In addition, 3749 (52.7%) respondents incorrectly attributed epilepsy to non-neurologic conditions, and 4865 (68.3%) respondents had an overall negative attitude toward people with epilepsy (PWE). They expressed objections to their child associating with PWE (2002; 28.1%) or their close relatives marrying PWE (3192; 44.8%), some believed that PWE are inferior (402; 5.6%), refused to hire a PWE (1126; 15.8%), and would feel discomfort around PWE (724; 10.3%). In addition, 2025 individuals (28.4%) believed that the health of PWE deteriorates over time; 1485 individuals (20.9%) believed that PWE get sick more often than others; 181 individuals (2.5%) believed that epilepsy could be transmitted; and 568 individuals (8.0%) believed that epilepsy could progress to malignant disease.ConclusionsIn Saudi Arabia, there is a substantial need for increasing the awareness and improving education on epilepsy in order to reduce stigma and increase the understanding of epilepsy. Such efforts could help improve the lives of people afflicted with the disease and ultimately contribute to better health outcomes for the entire community.

Evaluation of Paroxysmal Events in Critically Ill Patients: Relationship of Primary Diagnosis to Long-Term Electroencephalogram Yield.

Continuous EEG (cEEG) is indicated for the workup of paroxysmal events. We aimed to assess whether primary admission diagnoses predict the yield of cEEG when ordered for evaluating paroxysmal events. We identified patients in the ICU who underwent at least 6 hours of cEEG monitoring to evaluate paroxysmal events. Primary admission diagnoses were categorized into neurological or non-neurological conditions. cEEG results were dichotomized into presence or absence of epileptiform discharges. We identified 159 recordings that were obtained for the evaluation of paroxysmal events. Most patients (n = 100, 63%) were admitted with primary admission diagnoses of neurological disorders, such as ischemic stroke, or intracranial hemorrhage. We found that patients with primary neurological conditions were more likely to have brain surgeries, abnormal brain imaging, and focal neurological deficits on examination compared to those with primary non-neurological conditions. However, there was no significant difference in the prevalence of epileptiform discharges in cEEG among patients with primary diagnoses of neurological or non-neurological disorders. These results suggest that cEEG is often necessary to evaluate paroxysmal events, even among patients without primary neurological disorders.

Diagnosis and management of neurogenic orthostatic hypotension

Orthostatic hypotension is a sustained and pathological drop in blood pressure upon standing. Orthostatic hypotension can be due to non-neurogenic conditions or autonomic disorders. Impaired baroreflex-mediated vasoconstriction and insufficient release of norepinephrine play key roles in the pathophysiology of neurogenic orthostatic hypotension. Its common symptoms mainly related to inadequate cerebral blood flow include dizziness, lightheadedness, and syncope. It is crucial to differentiate neurogenic orthostatic hypotension from non-neurogenic orthostatic hypotension. For the management of neurogenic orthostatic hypotension, physicians should implement non-pharmacological methods and, if possible, reverse combined non-neurological conditions. Depending on severity of symptoms, pharmacological intervention may be tried after or with non-pharmacological methods. Its management should be individualized based on intensity of symptoms, comorbid conditions, drug side effects, and etiology. In this review, we discuss the definition, pathophysiology, clinical approach, and management of neurogenic orthostatic hypotension.

Clay-Polymer Nanocomposites Mediated Inhibition of Protein Aggregation: Possible Role in the Prevention of Proteinopathies.

The transformation of proteins from their native conformation into highly ordered fibrillar structures due to their misfolding and aggregation under particular conditions are described as beta-sheet enriched amyloid fibrils. The accumulation of these fibrils in different body parts is the major cause of several neurological and non-neurological conditions (proteinopathies). To prevent these proteinopathies, inhibition of protein aggregation is considered a promising strategy. Therefore, in this study, we synthesized montmorillonite (MMT) based poly- orthophenylenediamine (PoPD) nanocomposites (NCs) and characterized their size and morphology due to their remarkable biological properties. Further, the effect of these nanocomposites on inhibition of fibril formation was assessed. These nanocomposites were evaluated for their anti-amyloidogenic potential on two model proteins of amyloidopathies, i.e., human lysozyme and human serum albumin (HL & HSA), by using several biophysical methods, such as Thioflavin T (ThT) and 1-anilino-8-naphthalene sulfonate (ANS) fluorescence, congo red dye binding assay (CR). Secondary structural content was evaluated by Circular dichroism (CD) spectroscopy. Results demonstrated that synthesized nanocomposites significantly inhibited fibril formation in dose-dependent manner that corresponds to their ability to arrest fibrillation. It is suggested that they may adsorb proteins to protect them against aggregation when they are subjected to aggregating conditions. This study offers an opportunity to understand the mechanism of inhibition of fibril formation by nanocomposites, showing that they inhibit amyloid formation and amyloid diseases. Thus, the study concludes that these nanocomposites are promising candidates as therapeutic molecules for proteinopathies and are envisaged to enrich the area of personalized medicine, augmenting the human healthcare system.

Transforming Drug Development for Neurological Disorders: Proceedings from a Multidisease Area Workshop

Neurological disorders represent some of the most challenging therapeutic areas for successful drug approvals. The escalating global burden of death and disability for such diseases represents a significant worldwide public health challenge, and the rate of failure of new therapies for chronic progressive disorders of the nervous system is higher relative to other non-neurological conditions. However, progress is emerging rapidly in advancing the drug development landscape in both rare and common neurodegenerative diseases. In October 2022, the Critical Path Institute (C-Path) and the US Food and Drug Administration (FDA) organized a Neuroscience Annual Workshop convening representatives from the drug development industry, academia, the patient community, government agencies, and regulatory agencies regarding the future development of tools and therapies for neurological disorders. This workshop focused on five chronic progressive diseases: Alzheimer's disease, Parkinson's disease, Huntington's disease, Duchenne muscular dystrophy, and inherited ataxias. This special conference report reviews the key points discussed during the three-day dynamic workshop, including shared learnings, and recommendations that promise to catalyze future advancement of novel therapies and drug development tools.

Antiseizure Medications for the Prophylaxis of Migraine during the Anti- CGRP Drugs Era.

Migraine and epilepsy are fundamentally distinct disorders that can frequently coexist in the same patient. These two conditions significantly differ in diagnosis and therapy but share some widely- used preventive treatments. Antiseizure medications (ASMs) are the mainstay of therapy for epilepsy, and about thirty different ASMs are available to date. ASMs are widely prescribed for other neurological and non-neurological conditions, including migraine. However, only topiramate and valproic acid/valproate currently have an indication for migraine prophylaxis supported by high-quality evidence. Although without specifically approved indications and with a low level of evidence or recommendation, several other ASMs are used for migraine prophylaxis. Understanding ASM antimigraine mechanisms, including their ability to affect the pro-migraine calcitonin gene-related peptide (CGRP) signaling pathway and other pathways, may be instrumental in identifying the specific targets of their antimigraine efficacy and may increase awareness of the neurobiological differences between epilepsy and migraine. Several new ASMs are under clinical testing or have been approved for epilepsy in recent years, providing novel potential drugs for migraine prevention to enrich the treatment armamentarium and drugs that inhibit the CGRP pathway.

Predicting Alzheimer’s Disease from Clinical Dementia Rating, Estimated Total Intracranial Volume, Atlas Scaling Factor: Incorporating Ensemble Approach into Automated Machine Learning (P12-6.010)

<h3>Objective:</h3> With artificial intelligence (particularly machine learning) exhibiting superior predictive and prognosticative capabilities when compared with conventional statistical techniques, for neurological as well as non-neurological conditions, we explored automated Machine Learning to predict AD using variables such as socioeconomic status, Normalized Whole Brain Volume and Atlas Scaling Factor. <h3>Background:</h3> Alzheimer’s Disease (AD) is a debilitating disease associated with the pathognomonic deposition of neurofibrillary tangles and neuritic plaques along with characteristic amyloid angiopathy-driven hippocampal granulovacuolar degeneration and Meynert’s nucleus neuronal loss. <h3>Design/Methods:</h3> The data was adopted as shared on Kaggle. The study population comprised 373 human subjects (Female subjects = 57%; Range of age = 60–98). Variables include years of education, socioeconomic status and MMSE scores. The current state of the art for aML was adopted to develop classification models using algorithms including Extreme Gradient Boosting, Random Forest and Neural Network. The models were stacked after implementation of hyperparameter tuning, via insertion of random features and boosting on errors. Ensemble approach, which is the amalgamation of two or more than two algorithmic models to develop a model better than either of its computive components, was superimposed on stacked models. The mwA-AUROC area gauged the discriminating ability of models, with the highest value of 1 indicating perfect discriminative classification ability. <h3>Results:</h3> An ensemble of CatBoost, Nearest Neighbours and Neural Network algorithmic models with incorporated K-means features and boost on errors achieved an mwA-AUROC of 0.96 with a close-to perfect AD detection score. The respective model did not perform well in classifying converted patients. The ensemble model exhibited the least log loss among all developed algorithmic models. <h3>Conclusions:</h3> Such predictive models, when deployed on cloud, would serve to improve the management of the respective patient as well as the resource allocation, ultimately translating into significant reduction of morbidity and mortality associated with this enfeebling condition. <b>Disclosure:</b> Mr. Bangash has nothing to disclose. Miss Batool has nothing to disclose.

Hiccups, Hypersalivation, Hallucinations in Parkinson's Disease: New Insights, Mechanisms, Pathophysiology, and Management.

Parkinson's disease (PD) is a chronic, progressive neurological disorder and the second most common neurodegenerative condition. We report three common but overlooked symptoms in PD-hiccups, hypersalivation, and hallucinations-in terms of their prevalence, pathophysiology, and up-to-date evidence-based treatment strategies. Whilst all these three symptoms do occur in many other neurological and non-neurological conditions, early recognition and treatment are paramount. Whilst hiccups affect 3% of healthy people, their rate of occurrence is higher (20%) in patients with PD. Hypersalivation (Sialorrhea) is another common neurological manifestation of many neurological and other neurodegenerative conditions such as motor neuron disease (MND), with a median prevalence rate of 56% (range: 32-74%). A 42% prevalence of sialorrhea is also reported in sub-optimally treated patients with PD. Hallucinations, especially visual hallucinations, are commonly reported, with a prevalence of 32-63% in PD, and a 55-78% prevalence is noted in patients with dementia with Lewy bodies (DLB), followed by tactile hallucinations, which are indicated by a sensation of crawling bugs or imaginary creatures across the skin surface. Whilst mainstay and primary management strategies for all these three symptoms are carried out through history taking, it is also essential to identify and treat possible potential triggers such as infection, minimise or avoid causative (such as drug-induced) factors, and especially carry out patient education before considering more definitive treatment strategies, such as botulinum toxin therapies for hypersalivation, to improve the quality of life of patients. This original review paper aims to provide a comprehensive overview of the disease mechanisms, pathophysiology, and management of hiccups, hypersalivation, and hallucinations in Parkinson's disease.

Quantifying the effects of achilles tendon lengthening surgery: An intraoperative approach.

Achilles tendon lengthening (ATL) is frequently used in the treatment of foot deformities. However, there is currently no objective method to determine the optimal muscle length during surgery. We developed an intraoperative approach to evaluate the passive and active forces of the triceps surae muscle group before and after ATL and aimed to test the following hypotheses: 1) the ankle passive range of motion (ROM) increases, 2) passive muscle forces decrease post-ATL, and 3) forces measured from patients with non-neurological and neurological conditions demonstrate different characteristics. Passive forces at various ankle joint positions were measured in ten patients (11.3 ± 3.0years old) pre- and post-ATL using a force transducer attached to the Achilles tendon. In six patients, active isometric forces were measured by stimulating the triceps surae supramaximally. Passive forces decreased by 94.3% (p < 0.0001), and ROM increased by 89.4% (p < 0.0001) post-ATL. The pre-ATL passive forces were 70.8% ± 15.1% lower in patients with idiopathic foot deformities than in patients with neurological conditions (p < 0.001). The peak active force of 209.8 ± 114.3N was achieved at an ankle angle of 38.3° ± 16.0°, where the passive force was 6.3 ± 6.7N. The inter-individual variability was substantial in both groups. In conclusion, the hypotheses posed were supported. The present findings suggest that muscle passive and active force production as well as the inter-individual variability should be considered when planning further treatment.

Burden of illness among intermittent catheter users with non-neurogenic urinary retention in Denmark

ABSTRACT Background Urinary retention (UR) caused by non-neurogenic conditions is a frequent disorder often requiring the use of intermittent catheterization (IC). This study examines the burden of illness among subjects with an IC indication due to non-neurogenic UR. Methods Health-care utilization and costs were extracted from Danish registers (2002–2016) related to the first year after IC training and compared to matched controls. Results A total of 4,758 subjects with UR due to benign prostatic hyperplasia (BPH) and 3,618 subjects with UR due to other non-neurological conditions were identified. Total health-care utilization and costs per patient-year were significantly higher compared to matched controls (BPH: 12,406 EUR vs 4,363, p < 0.000; other non-neurogenic causes: 12,497 EUR vs 3,920, p < 0.000) and driven mainly by hospitalizations. Urinary tract infections (UTIs) were the most frequent bladder complications often requiring hospitalization. The inpatient costs per patient-year for UTIs were significantly higher for cases than controls (BPH: 479 EUR vs 31, p < 0.000; other non-neurogenic causes: 434 EUR vs 25, p < 0.000). Conclusions The burden of illness caused by non-neurogenic UR with need for IC was high and essentially driven by hospitalizations. Further research should clarify if additional treatment measures may reduce the burden of illness in subjects suffering from non-neurogenic UR using IC.

Recent Advances in the Discovery of Nicotinic Acetylcholine Receptor Allosteric Modulators.

Positive allosteric modulators (PAMs), negative allosteric modulators (NAMs), silent agonists, allosteric activating PAMs and neutral or silent allosteric modulators are compounds capable of modulating the nicotinic receptor by interacting at allosteric modulatory sites distinct from the orthosteric sites. This survey is focused on the compounds that have been shown or have been designed to interact with nicotinic receptors as allosteric modulators of different subtypes, mainly α7 and α4β2. Minimal chemical changes can cause a different pharmacological profile, which can then lead to the design of selective modulators. Experimental evidence supports the use of allosteric modulators as therapeutic tools for neurological and non-neurological conditions.

Conservative or liberal oxygen therapy for mechanically ventilated adults with acute brain pathologies: A post-hoc subgroup analysis.

To compare the effect of conservative vs. liberal oxygen therapy in mechanically ventilated adults in the intensive care unit (ICU) with non-hypoxic ischemic encephalopathy (HIE) acute brain pathologies. Post-hoc analysis of data from 217 patients with non-HIE acute brain pathologies included in the ICU Randomized Trial Comparing Two Approaches to OXygen therapy (ICU-ROX). Patients allocated to conservative oxygen spent less time with oxygen saturation ≥ 97% (50.5 [interquartile range (IQR), 18.5-119] vs. 82 h [IQR, 38-164], absolute difference, -31.5 h; 95%CI, -59.6 to -3.4). At 180 days, 38 of 110 conservative oxygen patients (34.5%) and 28 of 104 liberal oxygen patients (26.9%) had died (absolute difference, 7.6 percentage points; 95%CI, -4.7 to 19.9 percentage points; P = 0.23; interaction P = 0.02 for non-HIE acute brain pathologies vs. HIE; interaction P = 0.53 for non-HIE acute brain pathologies vs. non-neurological conditions). In this post-hoc analysis, patients admitted to the ICU with non-HIE acute brain pathologies treated with conservative oxygen therapy did not have significantly lower mortality than those treated with liberal oxygen. A trial with adequate statistical power is needed to determine whether our day 180 mortality point estimate of treatment effect favoring liberal oxygen therapy indicates a true effect.

Effect Modification between Genes and Environment and Parkinson's Disease Risk.

Parkinson's disease (PD) is a complex neurodegenerative condition in which genetic and environmental factors interact to contribute to its etiology. Remarkable progress has been made in deciphering disease etiology through genetic approaches, but there is limited data about how environmental and genetic factors interact to modify penetrance, risk, and disease severity. Here, we provide insights into environmental modifiers of PD, discussing precedents from other neurological and non-neurological conditions. Based on these examples, we outline genetic and environmental factors contributing to PD and review potential environmental modifiers of penetrance and clinical variability in monogenic and idiopathic PD. We also highlight the potential challenges and propose how future studies might tackle these important questions. ANN NEUROL 2022;92:715-724.

Optic Nerve Changes Detected with Ocular Ultrasonography during Different Surgical Procedures: A Narrative Review.

Ultrasonographic appraisal of the optic nerve sheath diameter has become popular in recent years as a useful diagnostic tool to detect intracranial pressure variations. Intracranial hypertension is a life-threatening disease with possible poor clinical outcomes and can be caused by a variety of neurological and non-neurological conditions. Considering the latter, increases in intracranial pressure have also been described during several surgical procedures. Ocular ultrasonography might be utilized to identify intracranial pressure increases by evaluating optic nerve sheath diameter variations. The aim of this review is to provide a wide overview on the use of the optic nerve ultrasound evaluation to detect intracranial pressure changes during surgical procedures, also discussing the pitfalls of the B-scan technique, the most widely used for such a purpose. PubMed medical database, Web of Science and Scopus were used to carry out this review. The present review showed that ocular ultrasonography could be considered a valuable diagnostic tool in the surgical setting to indirectly assess intracranial pressure. However, the use of the B-scan ultrasound should always be coupled with the standardized A-scan technique for a more accurate, precise and trustworthy ultrasound assessment.

Early Readmissions After Hospitalization for Posterior Reversible Encephalopathy Syndrome.

To evaluate the frequency, etiologies, and risk factors for 90-day readmissions after hospitalization for posterior reversible encephalopathy syndrome (PRES). Data were obtained from the Nationwide Readmissions Database 2016-2018. Patients with a primary diagnosis of PRES, survival to discharge, and known discharge disposition were included. The primary outcome was nonelective readmission within 90 days of discharge. Survival analysis was performed, and independent predictors of readmission were analyzed using multivariable Cox proportional hazards regression. Based on the study inclusion criteria, 6,155 eligible patients were included (mean ± SD age: 55.9 ± 17.3 years, female: 71.0%). Nonelective readmission within 90 days of discharge occurred for 1,922 (31.2%) patients. Of these, 617 readmissions were due to PRES-related or neurologic etiologies and the remaining 1,305 readmissions were due to non-neurologic conditions. In multivariable analysis, age was inversely associated with the risk of readmission (hazards ratio [HR] 0.92 for every 10 years increase in age, 95% CI 0.88-0.97). Patients with diabetes (HR 1.21, 95% CI 1.04-1.42), systemic lupus erythematosus (HR 1.42, 95% CI 1.03-1.96), acute kidney injury (HR 1.28, 95% CI 1.11-1.47), and a higher Charlson comorbidity index score (HR 1.09, 95% CI 1.06-1.13) were more likely to be readmitted. Furthermore, patients admitted at large bed size hospitals (HR 1.19, 95% CI 1.03-1.39), those with a longer length of stay (HR 1.01, 95% CI: 1.00-1.02), and those not discharged to home (HR 1.33, 95% CI: 1.14-1.55) during the index hospitalization were also at a higher risk for readmission. Nearly one-third of patients hospitalized because of PRES are readmitted within 90 days of discharge, and approximately one-third of these readmissions are due to PRES-related or neurologic etiologies. Younger age, a higher comorbidity burden, a longer length of hospital stay, and discharge disposition other than to home are independently associated with the risk of readmission.