Authors: Bahadar S. Srichawla, Maria A. Garcia-Dominguez, Brian Silver
Categories: Systematic Review, PRES, central variant, posterior reversible encephalopathy syndrome, systematic review, meta-analysis, posterior reversible leukoencephalopathy syndrome
Source: Neurology International
Authors: Bahadar S. Srichawla, Maria A. Garcia-Dominguez, Brian Silver
Background: The central variant of posterior reversible encephalopathy syndrome (cvPRES) is an atypical subtype of PRES. Although no unifying definitions exists, it is most often characterized by vasogenic edema involving “central” structures, such as the brainstem, subcortical nuclei, and spinal cord, with relative sparing of the parieto-occipital lobes. Methods: This systematic review and meta-analysis followed the PRISMA guidelines and was pre-registered on PROSPERO [CRD42023483806]. Both the Joanna Briggs Institute and New-Castle Ottawa scale were used for case reports and cohort studies, respectively. The meta-analysis was completed using R-Studio and its associated “metafor” package. Results: A comprehensive search in four databases yielded 70 case reports/series (n = 100) and 12 cohort studies. The meta-analysis revealed a pooled incidence rate of 13% (95% CI: 9–18%) for cvPRES amongst included cohort studies on PRES. Significant heterogeneity was observed (I^2^ = 71% and a τ
^2^ = 0.2046). The average age of affected individuals was 40.9 years, with a slightly higher prevalence in males (54%). The most common etiological factor was hypertension (72%). Fifty percent had an SBP >200 mmHg at presentation and a mean arterial pressure (MAP) of 217.6 ± 40.82. Imaging revealed an increased T2 signal involving the brain stem (88%), most often in the pons (62/88; 70.45%), and 18/100 (18%) cases of PRES with spinal cord involvement (PRES-SCI). Management primarily involved blood pressure reduction, with adjunctive therapies for underlying causes such as anti-seizure medications or hemodialysis. The MAP between isolated PRES-SCI and cvPRES without spinal cord involvement did not show significant differences (p = 0.5205). Favorable outcomes were observed in most cases, with a mortality rate of only 2%. Conclusions: cvPRES is most often associated with higher blood pressure compared to prior studies with typical PRES. The pons is most often involved. Despite the severity of blood pressure and critical brain stem involvement, those with cvPRES have favorable functional outcomes and a lower mortality rate than typical PRES, likely attributable to reversible vasogenic edema without significant neuronal dysfunction.
Posterior reversible encephalopathy syndrome (PRES) is a neurological disorder characterized by a variety of symptoms, including headaches, altered mental status, seizures, and visual disturbances. It is most identified through characteristic radiological findings, predominantly involving the posterior regions of the cerebral cortex and subcortical white matter [1]. Although the exact pathophysiology of PRES remains incompletely understood, it is thought to be related to endothelial dysfunction, leading to vasogenic edema. In recent years, a variant of this condition, known as central-variant PRES (cvPRES), has been increasingly recognized. Unlike the classical form of PRES, which predominantly affects the posterior regions of the brain, central-variant PRES is characterized by the involvement of central brain structures, including the basal ganglia, thalamus, brainstem, and/or spinal cord. This variation presents unique diagnostic challenges and may have different clinical implications compared to the typical form of PRES [2]. However, no unified consensus on the definition of cvPRES has been established.
cvPRES raises several critical questions about its epidemiology, clinical presentation, risk factors, pathophysiology, and outcomes. While there is growing literature on this subject, there has been no comprehensive synthesis of the evidence to date. Misdiagnosis or delayed diagnosis can lead to inappropriate management, potentially resulting in adverse outcomes. Understanding the distinct features of central-variant PRES, including its triggers, clinical course, and response to treatment, is crucial for optimizing patient care. Additionally, the location of vasogenic edema within the posterior fossa and brainstem brings forth the concern for life-threatening herniation syndromes, which may require decompressive craniectomy and other neurosurgical interventions.
In this systematic review and meta-analysis, we aim to provide a detailed analysis of the characteristics of cvPRES, comparing them with the classical form of the syndrome where relevant. We will evaluate aspects such as demographics, clinical manifestations, precipitating factors, imaging findings, medical and surgical management strategies, purported pathophysiological mechanisms, and outcomes. By doing so, we seek to offer a comprehensive overview of this condition, contributing to better recognition, diagnosis, and management of patients with central-variant PRES.
This study was exempt from an institutional review board, as it involves analysis of de-identified data that have already been collected. Therefore, it will not be possible to trace the data presented back to individual patients.
A PRISMA directed systematic review and meta-analysis were planned and prospectively registered on PROSPERO [CRD42023483806] and Open Science Framework (OSF) [3]. A comprehensive literature search was conducted across four electronic databases, including PubMed/PubMed Central/MEDLINE, ScienceDirect, Scopus, and Hinari. The search strategy was designed to include a combination of keywords and MeSH terms related to “Posterior Reversible Encephalopathy Syndrome,” “PRES,” “central variant,” “brainstem variant,” and related terminologies. The complete search string and terminologies for each database are included in Table 1. The search was restricted to studies published in English from the inception of the database. Reference lists of identified articles were manually searched to ensure the inclusion of additional relevant studies. Both backwards and forward citation tracking was utilized, and a gray literature search was completed by reviewing the first 100 results on Google Scholar and Open Gray.
Studies were included if they met the following (1) patients diagnosed with central-variant PRES, as defined by imaging criteria, which include increased T2-weighted signal involving central structures (e.g., basal ganglia, thalamus, brainstem, cerebellum, and spinal cord) in the absence of significant cortical involvement; (2) articles reporting on clinical features, imaging findings, management, and outcomes; and (3) study designs including randomized controlled trials, cohort studies, case-control studies, and case reports/series. All cases were reviewed by board-eligible or certified adult neurologists. Articles only of the English language were included. Reviews, editorials, commentaries, and studies with insufficient data on central-variant PRES were excluded. Records published in non-peer reviewed journals were not included in the analysis.
First, the aggregate records from the initial search were exported to EndNote 21, and duplicate records were removed. Next, two reviewers (B.S.S. & M.A.G-D.) independently extracted data using the Rayyan QCRI web platform. Extracted information included study characteristics (author, year of publication, study design), patient demographics (age, gender), clinical presentations, imaging findings, management strategies, and outcomes. Discrepancies between reviewers were resolved through discussion or by consulting a third reviewer (B.S.).
The quality and risk of bias assessment was assessed using appropriate the Joanna Briggs Institute (JBI) assessment tool for case reports/series and the Newcastle–Ottawa Scale for observational studies. The JBI tool consists of eight items addressing different aspects of the methodological quality of case reports, including precise patient demographics, accurate diagnosis, objective measurements of intervention outcomes, and follow-up information. The quality and risk of bias assessment were conducted by two authors (B.S.S., M.A.G-D.); a third author was consulted (B.S.) for any discrepancy between reviewers.
Descriptive statistics were used to analyze the extracted data. Data were presented as mean ± standard deviation (SD) and as frequencies and percentages for categorical variables. In this study, we conducted a meta-analysis to estimate the incidence rate of cvPRES from cohort studies. The Shapiro–Wilk test was used to assess for normality. An unpaired t-test was used when comparing MAPs between cvPRES without spinal cord involvement (SCI) and PRES-SCI. The meta-analysis was conducted using R-Studio, employing the “metafor” package to pool the incidence rate across studies. We assessed heterogeneity among studies using the I^2^ statistic. To visualize the results, we generated forest plots to display the individual and pooled incidence rate with corresponding 95% confidence intervals. Funnel plots were used to assess publication bias, and Baujat plots were constructed to identify studies that contributed significantly to heterogeneity.
Although the data presented here and their corresponding analysis is declassified, the data sheet and document will be stored on a secure password-protected hard drive indefinitely. The ethical standards outlined by the Declaration of Helsinki will be upheld. No attempt will be made to identify individual patients.
A total of 1120 records were obtained. After removing duplicates, 912 records had their abstracts and titles screened. A total of 191 records were reviewed and assessed for eligibility for inclusion in the qualitative and quantitative synthesis. A PRISMA-guided flow diagram of record assessment is provided in Figure 1. Single case records and case series are presented in Table 2 [4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90]. Cohort studies are included in Table 3 [7,18,21,26,62,91,92,93,94,95].
A total of 70 records with 100 patients are included in the single-case analysis. A total of 12 cohort studies are included. The average age of reported cases was 40.9. Fifty-four of one hundred cases occurred in men and 46/100 in women. Fourteen cases were reported in patients < 18 years of age. The most reported medical history include hypertension (40/100; 40% of cases), chronic kidney disease/end stage renal disease (ESRD) (13/100; 13%), acute kidney injury (4/100; 4%), human immunodeficiency virus (HIV) (2/100), systemic lupus erythematosus (6/100; 6%), and other immunological conditions, including Sjogren disease, polyarteritis nodosa, and thrombotic thrombocytopenic purpura (4/100; 4%). One case of T-cell acute lymphoblastic leukemia (T-ALL) (1), neurofibromatosis type-1 (NF-1), and testicular carcinoma on bleomycin, etoposide, and cisplatin were observed.
The systolic blood pressure (SBP) on arrival ranged from 120 to 270 mmHg (median: 200). Fifty out of one hundred cases had an SBP >200 mmHg. The mean SBP was 202 ± 37.58 mmHg (range: 120–270), diastolic blood pressure (DBP) 124 mmHg ± 27.35 mmHg (range: 40–220), pulse pressure (PP) 77.7 ± 22.89 (range: 36–142), and mean arterial pressure (MAP) 217.6 ± 40.82 (range: 85.3–326.66). Nineteen cases had seizures, 42/100 had headaches, and 21/100 had visual disturbance, with alteration in mental status in 14/100, three with aphasia, and one with Anton-Babinski syndrome, and 6/100 had decreased level of consciousness. Neurological symptoms localizing to the posterior circulation (e.g., dysarthria, dysphagia, dysmetria, nausea, vomiting, nystagmus, vertigo, lower cranial nerve palsy, obtundation/comatose, etc.) were seen in 30% of cases.
MRI findings included T2/FLAIR hyperintensities or vasogenic edema involving the brainstem in 88/100 (62/88 pons, 21/88 midbrain, 22/88 medulla). Additionally, vasogenic edema was observed in other areas, including 38/100 cerebellum/cerebellar peduncle, 21/100 basal ganglia, 15/100 thalamus, and 18/100 cases involving the spinal cord (18/18 cervical cord lesion, 5/18 thoracic cord lesion). Eighteen percent of cases reported diffusion weighted imaging (DWI) hyperintensities with corresponding apparent diffusion coefficient (ADC) mapping hypointensities. Four reported susceptibility weighted imaging (SWI) hypointensities involving the bilateral thalami (1), basal ganglia (2) and pons (1), and cerebral white matter (1). These SWI findings are suggestive of chronic microbleeds due to hypertension. Shimizu et al. reported a case of pediatric T-ALL with significant vasogenic edema, diffusion restriction, and contrast enhancement within the cerebellum [68]. Yamagami et al. reported a case of central-variant PRES with associated hemorrhagic transformation involving the basal ganglia and thalamus [78]. Zhang et al. presented a case of brainstem PRES involving the pons with hemorrhagic conversion [80]. de Havenon et al. presented two cases of spinal cord PRES, which showed a central confluent lesion involving the entire spinal cord [81]. Agarwal et al. reported a pediatric case of PRES-SCI with leptomeningeal enhancement [88].
Cerebrospinal fluid analysis when completed was often normal; six cases reported elevated protein. Kachi et al. reported a case of central PRES secondary to Sjogren disease, which showed elevated SSA/B antibodies as well as elevated oligoclonal bands in CSF [41]. Decker et al. completed a cerebellar biopsy on a patient with hypertension-related central PRES and found fibrinoid change and perivascular infiltrates of mature lymphocytes [27]. The case by Yis et al. demonstrated an elevated IgG index of 0.9 (normal: <0.7) [96].
Medical management most often included blood pressure reduction and seizure management. Thirteen cases required renal-replacement therapy (RRT), one case required VA-ECMO after a cardiac arrest, one individual required plasma exchange for thrombotic thrombocytopenic purpura, and four patients were treated with intravenous methylprednisolone, often with an underlying autoimmune condition (i.e., SLE and Sjogren disease). Three cases required emergent external ventricular drain (EVD) placement, two individuals required suboccipital decompressive craniectomy, and there was one case of high cervical (C1) laminectomy. One patient was treated with erythropoietin, ferrous sulfate, and bicarbonate for metabolic acidosis from obstructive nephropathy leading to uremia [40]. The patient described by Vaysman et al. who was hypertensive and had SLE was treated with plasmapheresis [75]. The case by Shimizu et al. showed significant hypertension in a 10-year-old girl (>99th percentile) on a chemotherapy regimen for T-ALL including four doses of intravenous vincristine (1.5 mg/m^2^ ) and daunorubicin (30 mg/m^2^) given every week, eight doses of intramuscular L-asparaginase (5000 units/m^2^) administered every third day, daily oral dexamethasone (10 mg/m^2^/day for three weeks and subsequent taper), and a single dose of intrathecal cytarabine (30 mg), methotrexate (12 mg), and prednisolone (10 mg) administered on day five of treatment [68]. Yokoyama et al. reported a case of central-variant PRES secondary to blood pressure fluctuations from Guillain Barre syndrome (GBS) treated with intravenous immunoglobulin (IVIG) [79].
The most common purported causes were hypertension (72/100; 72%), eclampsia (2), renal failure/kidney disease (4), SLE (4), Sjogren disease (1) hypomagnesemia (1), immunotherapy (1), sulfasalazine (1), and GBS (1). The case by Chaudhari et al. reported central PRES in a one-week postpartum woman with no clear etiology [23]. The case by Sharma et al. reported a 7-year-old boy with grade IV vesicoureteral reflex with hypertension [67]. Chan et al. reported the case of a 4-year-old boy with hypertension from NF-1-related renal artery stenosis with prominent vasogenic edema involving the pons, medulla, cerebellar hemispheres, and complete spinal cord (cervical > thoracic) [87]. Marrone et al. reported a case of central-variant PRES due to hypertension secondary to renal-artery stenosis from paraaortic lymph node dissection [86]. The pediatric PRES-SCI case by Agarwal et al. occurred because of hypertension secondary to renal artery stenosis [88]. The PRES-SCI case presented by Choh et al. occurred due to hypertension from IgA nephropathy [89]. Srichawla et al. reported a case of cvPRES due to rapidly fluctuating blood pressure presumedly from adrenal insufficiency [95]. Most cases showed clinical and radiographic improvement in 1–2 months from the initial diagnosis. We report a mortality rate of 2%; all cases succumbed to the illness and died within the same hospitalization.
Ahn et al. (2004) completed a single-center retrospective analysis of PRES and reported a prevalence of 4/37, 10.8% of the central-variant of PRES. Bansal et al. (2020) described 22 cases of PRES, wherein 40% had radiographic involvement of the cerebellum, 15% of the basal ganglia, 10% of the deep white matter, and 10% of the brainstem [7,18]. Brewer et al. (2013) performed a 10-year retrospective analysis on the neuroimaging findings of 47 women who had eclampsia. Eleven individuals (23%) were reported to involve the basal ganglia and cerebellum, five of whom were antepartum, and six were postpartum [97]. Chen et al. (2017) performed a retrospective analysis and found 11 individuals with the central variant of PRES (seven male and four female), with a median age of 60.0 (range 40.0–63.5). The reported etiology was hypertension in all eleven cases [91]. Chou et al. (2004) performed a retrospective analysis of 12 patients with clinical radiographic findings consistent with PRES [26]. Of the reported cases, 1/12 had radiographic findings consistent with the central variant (case 25). Fitzgerald et al. (2015) completed a retrospective review from 2007–2012 and identified 6/80 (7.5%) cases of central-variant PRES [92]. They determined a higher prevalence of extreme hypertension and renal dysfunction compared to the non-central variant [92]. Li et al. (2012) completed a retrospective study of 59 cases of PRES and reported the central variant occurring in five patients (brainstem n = 2; basal ganglia n = 3) [98]. McKinney et al. (2013) completed a retrospective review of 124 cases of PRES and determined 5/124 (4%) to have the central variant [2]. McKinney et al. (2007) completed another retrospective study of 76 PRES cases and determined that 30.3% involved the thalamus and 34.2% the cerebellum; 18.4% were within the brainstem, and 11.8% involved the basal ganglia [93]. Raman et al. (2017) completed a retrospective review of 92 patients with PRES and identified a total of 22 individuals with predominant brainstem and cerebellar involvement [99]. Yoon et al. completed a retrospective analysis of 16 PRES patients and found atypical radiographic findings including four episodes within the basal ganglia, three in the brainstem, two in the cerebellum, and three in the thalamus [100]. Aygunes et al. completed a retrospective review of 101 pediatric patients with PRES who underwent hematopoietic stem cell transplant [94]. They found a 15.8% (16/101) incidence of the central variant. They also noted a higher mortality rate (n = 10, 62.5%) compared to those with the typical variant (n = 5, 5.9%) [94].
A direct unpaired two-tailed t-test was performed to compare the mean arterial pressure (MAP) between isolated PRES with spinal cord involvement (PRES-SCI) and central-variant PRES without spinal cord involvement. Prior to the t-test, normality of the data was confirmed using the Shapiro–Wilk test, yielding W = 0.9329 and p = 0.2433, which passed the normality threshold with an α = 0.05. The unpaired t-test revealed no statistically significant difference in MAP between the two groups (t = 0.6453, p = 0.5205), suggesting that MAP levels are comparable in these presentations of PRES with spinal cord involvement. However, this may be limited by the smaller sample size in the PRES-SCI group (18 vs. 85).
The meta-analysis calculated the pooled incidence rate of the observed events (cvPRES) across the included studies. A total of eight studies that provided enough information on the incidence of the central variant of PRES was included in the quantitative synthesis. Using a random-effects model, the pooled incidence rate was estimated at 13% (CI: 9–18%) (Figure 2). Heterogeneity among studies was substantial, with an I^2^ = 71% and a τ^2^ = 0.2046. The heterogeneity was statistically significant (p < 0.01), indicating considerable variation in effect sizes across studies. To assess potential publication bias, a funnel plot was generated, and a Baujat plot was used to identify influential studies contributing to heterogeneity (Figure 3 and Figure 4).
The methodological quality and risk of bias for the included studies were assessed using the Joanna Briggs Institute (JBI) critical appraisal tool. Of the studies evaluated, the majority (n = 79) achieved a perfect score (8/8), indicating high methodological rigor and a low risk of bias. These studies consistently satisfied all eight appraisal criteria, demonstrating robustness in study design and reporting. Three studies received scores of 6/8 or 5/8, reflecting a moderate risk of bias due to unmet criteria in areas such as follow-up completeness or consideration of confounding factors. These studies include Arai et al. (1997), Braatz et al. (2014), and Matsumoto et al. (2014) [10,21,51]. Two studies (Doi et al., Resorlu et al.) scored 4/8, corresponding to a high risk of bias and potential limitations in methodological quality (Table 3) [63,101]. Overall, the quality assessment demonstrates that the included studies are predominantly of high methodological quality, with a small subset requiring caution in interpretation due to moderate to high risks of bias.
The quality of included cohort studies was assessed using the Newcastle–Ottawa Scale (NOS), which evaluates selection (maximum 4 points), comparability (maximum 2 points), and outcomes (maximum 3 points). A total score of 9 indicates the highest quality. Many of the studies (n = 10) achieved scores of 8 or 9, indicating robust methodological quality. Notably, Chen et al. (2017) scored the maximum 9 points, meeting all criteria across selection, comparability, and outcomes [91]. Other studies, including Ahn et al. (2004), Brewer et al., and Chou et al. (2004), consistently scored 8, reflecting strong performance in most domains [7,26,97]. One study, Bansal et al. (2020), scored 4 points [18]. While it demonstrated adequacy in selection (3 points) and outcome (1 point), it lacked comparability between cohorts, which significantly impacted its total score (Table 4).
The findings of this systematic review and meta-analysis provide a comprehensive understanding of the clinical, radiographic, and management characteristics of cvPRES, a rare but significant subtype of PRES. With an overall pooled incidence rate of 13% (95% CI: 9–18%) across cohort studies, our results underscore the clinical importance of recognizing this variant in settings where its presentation may deviate from the typical posterior-predominant PRES. In a study by Fugate et al., the mean peak systolic blood pressure among PRES patients was 199 mm Hg (range: 160–268 mm Hg), and the mean peak diastolic blood pressure was 109 mm Hg (range: 60–144 mm Hg) [102]. Another study by Rabinstein et al. reported that approximately 75% of PRES patients presented with hypertension, indicating that while elevated blood pressure is common, it is not a universal finding in PRES cases [103]. They reported a mean SBP of 182 ± 20 mm Hg and MAP 124 ± 15 [103]. In our cohort of 100 patients with cvPRES, we reported a higher mean SBP and MAP at 202 ± 37.58 mmHg and 217.6 ± 40.82, respectively.
The higher blood pressure observed in cvPRES compared to typical PRES may suggest a distinct pathophysiological mechanism potentially driven by differential vascular autoregulatory thresholds in central brain structures. Unlike the posterior cortex, which has relatively low autoregulatory capacity and is prone to vasogenic edema at moderate elevations in blood pressure, the brainstem, basal ganglia, and thalamus may require more extreme hypertension to surpass their autoregulatory limits [104]. This could explain the selective involvement of these regions in central-variant PRES. Furthermore, the proximity of these structures to deep perforating arteries with limited collateral flow may exacerbate vulnerability under conditions of severe hypertension, leading to more profound endothelial dysfunction, breakdown of the blood-brain barrier, and vasogenic edema [105]. Excessive adrenergic stimulation may amplify vascular permeability and inflammatory responses in central brain regions. Additionally, the co-occurrence of microvascular compromise or pre-existing structural abnormalities, such as chronic hypertension-induced arteriolosclerosis, could heighten susceptibility to central-variant manifestations. However, these hypotheses need to be supported by original studies.
In our dataset, the pons was predominantly affected, which may be attributed to several pathophysiological mechanisms underlying reversible pontine edema. The pons, a critical structure within the brainstem, is particularly susceptible to fluctuations in blood pressure due to its unique vascular supply and limited sympathetic innervation [106]. Acute hypertension can overwhelm the autoregulatory capacity of the pontine vasculature, leading to endothelial dysfunction and increased permeability of the blood-brain barrier [107]. Furthermore, the anatomical configuration of the pons, with its dense arrangement of neural tracts and nuclei, may predispose it to the accumulation of interstitial fluid during episodes of increased vascular permeability [52]. The resultant edema can disrupt neural conduction, leading to the clinical manifestations observed in patients with pontine involvement. Most notably, patients with cvPRES rarely reported diffusion restriction or cytotoxic edema within the pons. Thus, the impaired autoregulation does not lead to irreversible neuronal injury and permanent neurological deficits, which may be seen in a pontine stroke or central pontine myelinolysis [108].
This review has several limitations. First, the included studies predominantly consisted of case reports and small retrospective cohort studies, limiting the generalizability of our findings. The heterogeneity observed (I^2^ = 71%, τ^2^ = 0.2046) suggests variability in study designs, diagnostic criteria, and patient populations. Our meta-analysis attempts to address this through random-effects modeling. Additionally, publication bias may have influenced our results, as suggested by the asymmetry in the funnel plot and influential studies identified in the Baujat plot. The reliance on English-language studies may also introduce selection bias. Although we show that cvPRES has a higher mean MAP compared to isolated PRES seen in other studies, head-to-head studies needs to be completed to validate this. Further research is needed to better elucidate the pathophysiology and optimal management of central-variant PRES. Prospective studies with larger sample sizes and standardized diagnostic criteria are essential to validate our findings and explore the impact of specific interventions on patient outcomes. Symptoms and clinical characteristics of cvPRES appear to be similar to those of normal PRES; however, this should be studied using a comparator group. Moreover, longitudinal studies examining the long-term cognitive and functional sequelae of central-variant PRES could provide valuable insights into its prognosis. Finally, the integration of advanced hemodynamic monitoring, particularly those techniques that can measure the rate of MAP changes to estimate cerebral perfusion pressure and autoregulatory changes within the cerebral vasculature, will be necessary to identify the exact pathophysiological underpinnings of cvPRES compared to its typical clinico-radiographic presentation.
Central-variant PRES (cvPRES) manifests predominantly in younger adults with severe hypertension, most often involving the pons and other central structures (i.e., subcortical nuclei, brainstem, cerebellum, and spinal cord), and has a pooled incidence rate of 13% amongst cohort studies of PRES. Despite higher blood pressures and critical brainstem edema, outcomes are generally favorable (2% mortality), reflecting reversible vasogenic injury rather than permanent neuronal damage. Cases of cvPRES have a higher MAP compared to that what is reported in the literature of typical PRES. However, this needs to be supported with original studies. Early recognition of its distinctive imaging pattern and prompt blood-pressure management are key to optimizing recovery. Future prospective studies should standardize diagnostic criteria, elucidate underlying autoregulatory mechanisms, and evaluate targeted interventions to further improve patient outcomes.