The research team, led by Jocelyn Cruz-Perez and senior author Daniel San-Juan, identified patients through electronic medical records and applied the definition of status epilepticus established by the International League Against Epilepsy, the global body whose 2015 task force formalized both a time-based definition—roughly five minutes of continuous seizure activity for most seizure types—and a framework for classifying the condition by its cause and clinical features. Every patient included was at least eighteen years old and met criteria for refractory disease, meaning their seizures persisted despite appropriate first- and second-line antiseizure drug therapy. The investigators collected a wide sweep of clinical information for each patient: demographics, prior neurological history, imaging findings, laboratory values, electroencephalography recordings, medication exposures, duration of mechanical ventilation, length of hospital stay, and functional status at discharge from the neurological intensive care unit.

The demographic picture was striking for its youth. The median age of patients was just 34 years, with an interquartile range of 26 to 44, and 52.9 percent of the cohort were women. This is considerably younger than the typically elderly populations described in many high-income country series, where cerebrovascular disease and neurodegenerative conditions dominate the seizure landscape, and it reflects a different underlying epidemiology. In the Mexican cohort, 70.6 percent of patients had preexisting epilepsy before their refractory episode, while the remaining 29.4 percent experienced what clinicians call new-onset refractory status epilepticus, a seizure emergency erupting in a person with no prior diagnosis. When the researchers stratified their analysis by these two groups, as they had prespecified, important differences in both etiology and outcome emerged.

The leading causes of refractory episodes fell into three broad categories. Infections accounted for 23.5 percent of cases, structural and vascular causes—spanning strokes, tumors, and other focal brain lesions—accounted for 22.5 percent, and treatment-related factors, typically antiseizure medication withdrawal or inadequate drug levels in people with known epilepsy, accounted for 16.7 percent. The prominence of infectious etiologies, a pattern echoed in other series from low- and middle-income countries, underscores what the authors describe as preventable or modifiable contributors to catastrophic seizure emergencies. Central nervous system infections such as neurocysticercosis, a parasitic condition endemic to parts of Latin America, remain significant drivers of acute seizures in the region, and interrupted access to antiseizure medication is a well-documented trigger for breakthrough episodes in people with established epilepsy.

Electroencephalography, the cornerstone of diagnosis and monitoring in status epilepticus, most commonly revealed diffuse slowing of background rhythms in these patients, a finding associated with severe encephalopathic states. Interictal epileptiform discharges—the sharp, stereotyped waveform abnormalities that betray a brain prone to seizures—appeared in 27.7 percent of recordings. The reliance on EEG in this cohort highlights a persistent challenge in intensive care neurology: non-convulsive status epilepticus, in which the brain continues seizing electrically without visible convulsions, can only be detected by electroencephalography, and in resource-limited settings the availability of continuous EEG monitoring is often limited. The study’s institution, as Mexico’s national neurological referral center, represents one of the better-equipped environments in the country, yet the heterogeneity of monitoring documented in the series illustrates the practical constraints under which clinicians operate.

Treatment was markedly heterogeneous, mirroring the absence of a single universally validated protocol for refractory disease. An overwhelming 82.4 percent of patients required third-line therapy, typically continuous infusion of anesthetic agents such as midazolam, propofol, or ketamine, aimed at suppressing electrical seizure activity while systemic complications were managed in parallel. The median hospital stay stretched to 21.5 days, and patients spent an average of 8 days on mechanical ventilation—figures that convey the enormous intensity of care these episodes demand. Respiratory support, hemodynamic management, and prolonged sedation carry their own complications, and the burden of illness associated with super-refractory and prolonged disease is well recognized in the international literature as both clinically severe and economically significant. One patient in the cohort underwent surgery—resective neurosurgery directed at the epileptic focus—without complications, a reminder that in carefully selected cases, operative intervention can be part of the rescue arsenal when pharmacological strategies fail.

Perhaps the most encouraging finding was that despite the severity of the condition, resolution of status epilepticus was achieved in 87.3 percent of patients. That figure challenges a fatalistic view of refractory disease and aligns with emerging international evidence that aggressive, protocolized treatment can terminate even stubborn seizure emergencies, particularly in younger patients whose brains retain compensatory reserve. Functional outcomes at intensive care discharge, measured with the modified Rankin Scale—the ordinal scale from zero, indicating no symptoms, to six, indicating death—told a more nuanced story. While many patients left the unit with favorable functional status, unfavorable scores were significantly associated with preexisting epilepsy in the stratified analysis.

That association proved to be one of the study’s most clinically informative threads. Patients with preexisting epilepsy were significantly more likely to have experienced prior episodes of status epilepticus, more likely to achieve seizure resolution, paradoxically more likely to have an unfavorable modified Rankin Scale at discharge, and carried significantly higher scores on both the STESS and END-IT prognostic instruments. The Status Epilepticus Severity Score, developed by Rossetti and colleagues, incorporates age, seizure type, level of consciousness, and history of prior seizures to estimate outcome, while the END-IT score adds etiology, non-convulsive status, and mechanical ventilation to the prognostic equation. The finding that higher END-IT scores correlated with the need for third-line treatment suggests these prognostic tools may also help clinicians anticipate resource requirements—predicting which patients will need anesthetic infusions, prolonged ventilation, and extended intensive care bed occupancy.

The authors are careful to frame their findings within the limitations inherent to a retrospective single-center design, acknowledging that treatment decisions were made by individual treating teams over twelve years and were not standardized, and that follow-up extended only to intensive care discharge rather than long-term neurological outcome. Yet the value of the work lies precisely in its real-world texture. Systematic reviews of status epilepticus management in resource-limited settings have repeatedly identified a scarcity of local evidence as a barrier to guideline development, with most contemporary treatment algorithms derived from European and North American cohorts. Studies from India, Honduras, Morocco, and the Philippines have begun to fill that gap, and this Mexican series adds a substantial contribution from Latin America, a region where epilepsy care infrastructure varies widely and where antiseizure medication availability remains uneven, as documented by the International League Against Epilepsy’s own Task Force on Access to Treatment.

The broader message from the Mexican cohort is twofold. First, refractory status epilepticus in a tertiary Latin American setting is driven disproportionately by young patients, by preexisting epilepsy, and by infectious and treatment-related triggers—many of which are potentially preventable through better medication access, adherence support, and infection control. Second, even in a resource-constrained environment, the majority of these emergencies can be resolved, and favorable functional outcomes are often achievable. The study’s authors dedicate their findings, in part, to the multidisciplinary critical care teams whose work sustained patients through episodes lasting weeks. For a condition in which every minute of ongoing seizure activity compounds neuronal injury—the principle encapsulated in the aphorism that time is brain—the demonstration that 87.3 percent of refractory episodes ended in seizure cessation represents not merely a statistical result, but a proof of feasibility for intensive epilepsy care in settings long assumed to lack the capacity for it. Future work, the researchers suggest, should extend observation beyond discharge, standardize treatment protocols, and build multicenter networks across Latin America so that the next generation of evidence can guide policy as well as practice.

Psoriasis, a chronic autoimmune skin disorder, is characterized by the rapid proliferation of skin cells, leading to scaling and inflammation. Traditional therapies often focus on symptomatic relief but may come with undesirable side effects or variable efficacy among patients. This study presents an innovative approach by exploring the potential of hydralazine, traditionally used to treat high blood pressure, in addressing the root cause of psoriasis via epigenetic modulation.

The primary focus of this extensive study was to investigate the epigenetic mechanisms influenced by hydralazine, particularly its ability to modify gene expression without altering the underlying DNA sequence. By analyzing real-world patient data, the researchers sought to determine if those treated with hydralazine exhibited altered clinical outcomes for psoriasis compared to traditional treatments. This 16-year retrospective cohort study is among the first of its kind, adding significant weight to the argument for drug repurposing in dermatology.

One of the standout findings from this landmark study was the surprising normalization of cutaneous gene expression patterns in patients undergoing hydralazine treatment. By examining skin biopsies and clinical presentations, the researchers found that hydralazine could impact crucial pathways related to inflammation and hyperproliferation of keratinocytes, the primary cell type in the epidermis. This change at the molecular level has the potential to redefine the therapeutic landscape for psoriasis, which has long been characterized by a limited arsenal of effective treatment options.

The data showcased in Wu et al.’s study demonstrated that patients treated with hydralazine reported marked improvements in their psoriasis symptoms. This includes reduced plaque formation, decreased itching, and a lower incidence of psoriatic arthritis, a comorbid condition that complicates the lives of many psoriasis sufferers. Such results not only provide hope for patients seeking relief but also invite further investigation into the underside of hydralazine’s mode of action at an epigenetic level.

The implications of repurposing hydralazine extend beyond immediate clinical benefits. With increasing concerns regarding the safety profiles and accessibility of traditional systemic therapies, as well as the high costs associated with biologic treatments, this study holds the promise of both affordability and efficacy. For many patients, the idea of utilizing an existing medication with a well-documented safety history is immensely reassuring and potentially revolutionary.

Further, this research emphasizes the necessity for incorporating real-world evidence into clinical practice, shedding light on how everyday medications can be viewed through a new lens. By leveraging historical patient data, the researchers advocate for a more dynamic approach to treatment wherein existing drugs are reassessed and repurposed based on emerging insights into their pharmacodynamics and potential off-target effects.

Although the findings are promising, Wu and colleagues urge caution, highlighting the necessity for randomized controlled trials to validate the results of their retrospective analysis. Such studies would further elucidate the mechanisms through which hydralazine mediates its effects and establish robust clinical guidelines for its application in psoriasis treatment.

In addition to exploring hydralazine’s epigenetic properties, the researchers acknowledged potential molecular pathways, such as the modulation of histone acetylation and DNA methylation, that may play a crucial role in the development of psoriasis. Gaining a deeper understanding of these pathways could pave the way for more targeted epigenetic therapies in the future.

Moreover, the complex interplay between genetics, environment, and epigenetic factors in the development of psoriasis presents an intriguing avenue for future research. As the field continues to unravel the various layers of pathogenic mechanisms, drugs like hydralazine could find prominent positions in a multifaceted treatment strategy that addresses not only symptoms but also underlying causes.

The enthusiasm surrounding these findings was palpable among the medical community, particularly given the growing interest in repurposing existing medications for new therapeutic uses. The fundamental shift towards evidence-based practice, embracing data from various sources, signifies an evolution in the way researchers and practitioners view disease management. Reports such as this one could soon become catalysts for transformative change in dermatological care.

As we look ahead, the ongoing investigation into repurposing established medications such as hydralazine underscores a fundamental truth in medicine: existing therapies may serve uncharted paths that extend beyond their original indications. Thus, the exploration into hydralazine’s role as an epigenetic modulator could mark a significant leap forward in the quest for innovative solutions to chronic conditions like psoriasis.

In summary, Wu’s study sets an important precedent for the future of psychiatric disease management. By harnessing both the power of real-world evidence and the potential of drug repurposing, this research highlights not just a novel treatment avenue but an entirely new perspective on existing medications in the fight against stubborn ailments like psoriasis. With the healthcare landscape continuously evolving, the implications of this study may resonate far beyond the confines of dermatology, potentially reaching diverse areas that could benefit from a similar approach.

Subject of Research: Repurposing hydralazine as a potential epigenetic modulator for psoriasis.

Article Title: Real-world evidence for repurposing hydralazine as a potential epigenetic modulator for psoriasis: a 16-year retrospective nationwide cohort study.

Article References:

Wu, SE., Wang, W., Hung, CT. et al. Real-world evidence for repurposing hydralazine as a potential epigenetic modulator for psoriasis: a 16-year retrospective nationwide cohort study.
J Transl Med 23, 1296 (2025). https://doi.org/10.1186/s12967-025-07322-4

Image Credits: AI Generated

DOI: https://doi.org/10.1186/s12967-025-07322-4

Keywords: Hydralazine, psoriasis, epigenetic modulation, drug repurposing, retrospective cohort study.