Cytokines in New-Onset Refractory Status Epilepticus Predict Outcomes.

OBJECTIVE: The objective of this study was to investigate inflammation using cerebrospinal fluid (CSF) and serum cytokines/chemokines in patients with new-onset refractory status epilepticus (NORSE) to better understand the pathophysiology of NORSE and its consequences. METHODS: Patients with NORSE (n = 61, including n = 51 cryptogenic), including its subtype with prior fever known as febrile infection-related epilepsy syndrome (FIRES), were compared with patients with other refractory status epilepticus (RSE; n = 37), and control patients without SE (n = 52). We measured 12 cytokines/chemokines in serum or CSF samples using multiplexed fluorescent bead-based immunoassay detection. Cytokine levels were compared between patients with and without SE, and between the 51 patients with cryptogenic NORSE (cNORSE) and the 47 patients with a known-etiology RSE (NORSE n = 10, other RSE n = 37), and correlated with outcomes. RESULTS: A significant increase of IL-6, TNF-α, CXCL8/IL-8, CCL2, MIP-1α, and IL-12p70 pro-inflammatory cytokines/chemokines was observed in patients with SE compared with patients without SE, in serum and CSF. Serum innate immunity pro-inflammatory cytokines/chemokines (CXCL8, CCL2, and MIP-1α) were significantly higher in patients with cNORSE compared to non-cryptogenic RSE. Patients with NORSE with elevated innate immunity serum and CSF cytokine/chemokine levels had worse outcomes at discharge and at several months after the SE ended. INTERPRETATION: We identified significant differences in innate immunity serum and CSF cytokine/chemokine profiles between patients with cNORSE and non-cryptogenic RSE. The elevation of innate immunity pro-inflammatory cytokines in patients with NORSE correlated with worse short- and long-term outcomes. These findings highlight the involvement of innate immunity-related inflammation, including peripherally, and possibly of neutrophil-related immunity in cNORSE pathogenesis and suggest the importance of utilizing specific anti-inflammatory interventions. ANN NEUROL 2023;94:75-90.

History and evolution of surgical treatment for spasticity: a journey from neurotomy to selective dorsal rhizotomy.

The evolution of neurosurgical approaches to spasticity spans centuries, marked by key milestones and innovative practitioners. Probable ancient descriptions of spasmodic conditions were first classified as spasticity in the 19th century through the interventions of Dr. William John Little on patients with cerebral palsy. The late 19th century witnessed pioneering efforts by surgeons such as Dr. Charles Loomis Dana, who explored neurotomies, and Dr. Charles Sherrington, who proposed dorsal rhizotomy to address spasticity. Dorsal rhizotomy rose to prominence under the expertise of Dr. Otfrid Foerster but saw a decline in the 1920s due to emerging alternative procedures and associated complications. The mid-20th century saw a shift toward myelotomy but the revival of dorsal rhizotomy under Dr. Claude Gros' selective approach and Dr. Marc Sindou's dorsal root entry zone (DREZ) lesioning. In the late 1970s, Dr. Victor Fasano introduced functional dorsal rhizotomy, incorporating electrophysiological evaluations. Dr. Warwick Peacock and Dr. Leila Arens further modified selective dorsal rhizotomy, focusing on approaches at the cauda equina level. Later, baclofen delivered intrathecally via an implanted programmable pump emerged as a promising alternative around the late 1980s, pioneered by Richard Penn and Jeffrey Kroin and then led by A. Leland Albright. Moreover, intraventricular baclofen has also been tried in this matter. The evolution of these neurosurgical interventions highlights the dynamic nature of medical progress, with each era building upon and refining the work of significant individuals, ultimately contributing to successful outcomes in the management of spasticity.

The seasonality of new-onset refractory status epilepticus (NORSE).

The etiology of new-onset refractory status epilepticus (NORSE), including its subtype with prior fever known as FIRES (febrile infection-related epilepsy syndrome), remains uncertain. Several arguments suggest that NORSE is a disorder of immunity, likely post-infectious. Consequently, seasonal occurrence might be anticipated. Herein we investigated if seasonality is a notable factor regarding NORSE presentation. We combined four different data sets with a total of 342 cases, all from the northern hemisphere, and 62% adults. The incidence of NORSE cases differed between seasons (p = .0068) and was highest in the summer (32.2%) (p = .0022) and lowest in the spring (19.0%, p = .010). Although both FIRES and non-FIRES cases occurred most commonly during the summer, there was a trend toward FIRES cases being more likely to occur in the winter than non-FIRES cases (OR 1.62, p = .071). The seasonality of NORSE cases differed according to the etiology (p = .024). NORSE cases eventually associated with autoimmune/paraneoplastic encephalitis occurred most frequently in the summer (p = .032) and least frequently in the winter (p = .047), whereas there was no seasonality for cryptogenic cases. This study suggests that NORSE overall and NORSE related to autoimmune/paraneoplastic encephalitis are more common in the summer, but that there is no definite seasonality in cryptogenic cases.

Review and standard operating procedures for collection of biospecimens and analysis of biomarkers in new onset refractory status epilepticus.

New onset refractory status epilepticus (NORSE), including its subtype with a preceding febrile illness known as febrile infection-related epilepsy syndrome (FIRES), is one of the most severe forms of status epilepticus. The exact causes of NORSE are currently unknown, and there is so far no disease-specific therapy. Identifying the underlying pathophysiology and discovering specific biomarkers, whether immunologic, infectious, genetic, or other, may help physicians in the management of patients with NORSE. A broad spectrum of biomarkers has been proposed for status epilepticus patients, some of which were evaluated for patients with NORSE. Nonetheless, none has been validated, due to significant variabilities in study cohorts, collected biospecimens, applied analytical methods, and defined outcome endpoints, and to small sample sizes. The NORSE Institute established an open NORSE/FIRES biorepository for health-related data and biological samples allowing the collection of biospecimens worldwide, promoting multicenter research and sharing of data and specimens. Here, we suggest standard operating procedures for biospecimen collection and biobanking in this rare condition. We also propose criteria for the appropriate use of previously collected biospecimens. We predict that the widespread use of standardized procedures will reduce heterogeneity, facilitate the future identification of validated biomarkers for NORSE, and provide a better understanding of the pathophysiology and best clinical management for these patients.

Usefulness of Artificial Intelligence in Traumatic Brain Injury: A Bibliometric Analysis and Mini-review.

BACKGROUND: Traumatic brain injury (TBI) has become a major source of disability worldwide, increasing the interest in algorithms that use artificial intelligence (AI) to optimize the interpretation of imaging studies, prognosis estimation, and critical care issues. In this study we present a bibliometric analysis and mini-review on the main uses that have been developed for TBI in AI. METHODS: The results informing this review come from a Scopus database search as of April 15, 2023. The bibliometric analysis was carried out via the mapping bibliographic metrics method. Knowledge mapping was made in the VOSviewer software (V1.6.18), analyzing the "link strength" of networks based on co-occurrence of key words, countries co-authorship, and co-cited authors. In the mini-review section, we highlight the main findings and contributions of the studies. RESULTS: A total of 495 scientific publications were identified from 2000 to 2023, with 9262 citations published since 2013. Among the 160 journals identified, The Journal of Neurotrauma, Frontiers in Neurology, and PLOS ONE were those with the greatest number of publications. The most frequently co-occurring key words were: "machine learning", "deep learning", "magnetic resonance imaging", and "intracranial pressure". The United States accounted for more collaborations than any other country, followed by United Kingdom and China. Four co-citation author clusters were found, and the top 20 papers were divided into reviews and original articles. CONCLUSIONS: AI has become a relevant research field in TBI during the last 20 years, demonstrating great potential in imaging, but a more modest performance for prognostic estimation and neuromonitoring.

Seizure Assessment and Forecasting With Efficient Rapid-EEG: A Retrospective Multicenter Comparative Effectiveness Study.

BACKGROUND AND OBJECTIVES: Approximately 30% of critically ill patients have seizures, and more than half of these seizures do not have an overt clinical correlate. EEG is needed to avoid missing seizures and prevent overtreatment with antiseizure medications. Conventional-EEG (cEEG) resources are logistically constrained and unable to meet their growing demand for seizure detection even in highly developed centers. Brief EEG screening with the validated 2HELPS2B algorithm was proposed as a method to triage cEEG resources, but it is hampered by cEEG requirements, primarily EEG technologists. Seizure risk-stratification using reduced time-to-application rapid response-EEG (rrEEG) systems (∼5 minutes) could be a solution. We assessed the noninferiority of the 2HELPS2B score on a 1-hour rrEEG compared to cEEG. METHODS: A multicenter retrospective EEG diagnostic accuracy study was conducted from October 1, 2021, to July 31, 2022. Chart and EEG review performed with consecutive sampling at 4 tertiary care centers, included records of patients ≥18 years old, from January 1, 2018, to June 20, 2022. Monte Carlo simulation power analysis yielded n = 500 rrEEG; for secondary outcomes n = 500 cEEG and propensity-score covariate matching was planned. Primary outcome, noninferiority of rrEEG for seizure risk prediction, was assessed per area under the receiver operator characteristic curve (AUC). Noninferiority margin (0.05) was based on the 2HELPS2B validation study. RESULTS: A total of 240 rrEEG with follow-on cEEG were obtained. Median age was 64 (interquartile range 22); 42% were female. 2HELPS2B on a 1-hour rrEEG met noninferiority to cEEG (AUC 0.85, 95% CI 0.78-0.90, p = 0.001). Secondary endpoints of comparison with a matched contemporaneous cEEG showed no significant difference in AUC (0.89, 95% CI 0.83-0.94, p = 0.31); in false negative rate for the 2HELPS2B = 0 group (p = 1.0) rrEEG (0.021, 95% CI 0-0.062), cEEG (0.016, 95% CI 0-0.048); nor in survival analyses. DISCUSSION: 2HELPS2B on 1-hour rrEEG is noninferior to cEEG for seizure prediction. Patients with low-risk (2HELPS2B = 0) may be able to forgo prolonged cEEG, allowing for increased monitoring of at-risk patients. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that rrEEG is noninferior to cEEG in calculating the 2HELPS2B score to predict seizure risk.

Ernesto Bustamante Zuleta (1922-2021): pioneering teacher and practitioner of Colombian neurosurgery.

Ernesto Bustamante Zuleta (1922-2021) was an impactful Colombian neurosurgeon whose legacy is inextricably linked with the development of the neurosurgery specialty in Colombia. His detail-oriented approach to treatment complemented his reputation for mastery of the neurosciences. Never simply confined to the operating theater, this calm and considerate physician felt compelled to teach during his entire career. The result of his teaching made a lasting imprint on an entire generation of neurosurgeons who subsequently established a high standard of neurosurgical care in Colombia. A true pioneer, Bustamante comprehensively engaged in his field, from founding the country's first residency program in neurosurgery to successfully implementing technology in his procedures, performing many of Colombia's first neurosurgical interventions, and publishing extensively across various categories of medical science. This historical reflection highlights his enduring contributions to the field and considers his legacy through the witness testimony of many of his students and collaborators. The hope is that his contributions may be acknowledged in full, as he was a reserved person who never boasted of his own accomplishments. The authors also hope that those who did not have the opportunity to know him would be informed by the historical context of the development of Colombian neurosurgery and inspired by his conviction and altruism.

Neuropathology of New-Onset Refractory Status Epilepticus (NORSE).

New-Onset Refractory Status Epilepticus (NORSE), including its subtype with a preceding febrile illness known as FIRES (Febrile Infection-Related Epilepsy Syndrome), is one of the most severe forms of status epilepticus. Despite an extensive workup (clinical evaluation, EEG, imaging, biological tests), the majority of NORSE cases remain unexplained (i.e., "cryptogenic NORSE"). Understanding the pathophysiological mechanisms underlying cryptogenic NORSE and the related long-term consequences is crucial to improve patient management and preventing secondary neuronal injury and drug-resistant post-NORSE epilepsy. Previously, neuropathological evaluations conducted on biopsies or autopsies have been found helpful for identifying the etiologies of some cases that were previously of unknown cause. Here, we summarize the findings of studies reporting neuropathology findings in patients with NORSE, including FIRES. We identified 64 cryptogenic cases and 66 neuropathology tissue samples, including 37 biopsies, 18 autopsies, and seven epilepsy surgeries (the type of tissue sample was not detailed for 4 cases). We describe the main neuropathology findings and place a particular emphasis on cases for which neuropathology findings helped establish a diagnosis or elucidate the pathophysiology of cryptogenic NORSE, or on described cases in which neuropathology findings supported the selection of specific treatments for patients with NORSE.

A history of Colombian neurosurgery: events, persons, and outcomes that have shaped the specialty in the country.

The history of Colombian neurosurgery is a collective legacy of neurosurgeon-scientists, scholars, teachers, innovators, and researchers. Anchored in the country's foundational values of self-determination and adaptability, these pioneers emerged from the Spanish colonial medical tradition and forged surgical alliances abroad. From the time of Colombian independence until the end of World War I, exchanges with the French medical tradition produced an emphasis on anatomical and systematic approaches to the emerging field of neurosurgery. The onset of American neurosurgical expertise in the 1930s led to a new period of exchange, wherein technological innovations were added to the Colombian neurosurgical repertoire. This diversity of influences culminated in the 1950s with the establishment of Colombia's first in-country neurosurgery residency program. A select group of avant-garde neurosurgeons from this period expanded the domestic opportunities for patients and practitioners alike. Today, the system counts 10 recognized neurosurgery residency programs and over 500 neurosurgeons within Colombia. Although the successes of specific individuals and innovations were considered, the primary purpose of this historical survey was to glean relevant lessons from the past that can inform present challenges, inspire new opportunities, and identify professional and societal goals for the future of neurosurgical practice and specialization.

Weight Loss-associated Superior Mesenteric Artery Syndrome, an Unusual Condition in a Peruvian Patient: A Case Report.

Superior mesenteric artery syndrome (SMAS) is an uncommon cause of small bowel obstruction. We report a young male patient with abdominal pain, emesis and history of significant weight loss. Computed tomography angiography demonstrated narrowing of the aortomesenteric angle. The patient underwent conservative medical management, focusing on relieving obstruction and nutritional support.

La política científica cubana como una fortaleza para enfrentar la pandemia de la COVID-19 / Cuban scientific policy as a strength to face the COVID-19 pandemic

RESUMEN El cambio multidimensional que significó el proceso revolucionario cubano, permitió el desarrollo científico de la isla. El objetivo de este artículo es explicar la relación entre la política científica cubana y sus consecuentes fortalezas para el enfrentamiento a la pandemia de la COVID-19. Se revisaron varias investigaciones sobre la política científica cubana, la Biotecnología, los estudios actualizados sobre el enfrentamiento del mundo a la COVID-19, y la respuesta de Cuba. Se realizaron búsquedas bibliográficas en sitios de internet y libros impresos. Cuba, país en vías de desarrollo, históricamente se ha visto afectado por un sistema económico, comercial y político internacional desigual y excluyente. Aun así, cuenta con una política científica coherente y sistemática, que exhibe resultados no perfectos, pero respetables y honestos. A través de la ciencia y el Sistema de Salud, se puede decir que la respuesta cubana ante esta pandemia, ha sido, en lo fundamental, exitosa.

ABSTRACT The multidimensional change in the Cuban revolutionary process allowed the scientific development of the island. The objective of this article is to explain the relationship between the Cuban scientific policy and its consequent strengths to face the COVID-19 pandemic. Several investigations on Cuban scientific policy, Biotechnology, updated studies on the world's confrontation with COVID-19, and Cuba's response were reviewed. Bibliographic searches were carried out on Internet sites and printed books. Cuba, a developing country, has been historically affected by an unequal and exclusive international economic, commercial and political system. Even so, it has a coherent and systematic scientific policy, which exhibits results that are not perfect, but respectable and honest. Thanks to its Health System and the development of science, it can be said that the Cuban response to this pandemic has been, fundamentally, successful.

Towards Improving Hypertensive Patients Care: Pervasive Monitoring and Diagnosis Support.

Hypertension is the most common chronic condition dealt with by primary care physicians and other health practitioners. It usually has no symptoms, causing a delay in diagnosis. Moreover, around 20% of the global population suffers from "white-coat syndrome", which can lead to misdiagnosing hypertension. When diagnosed, patients find it difficult to constantly monitor their blood pressure to ensure it is within acceptable levels. In this work, we propose a pervasive solution model for ambulatory monitoring of hypertensive patients and for supporting a clinician with the task of diagnosing hypertension. It contributes to the selection of attributes and techniques for assisting hypertension diagnosis, and also to an implementation which dynamically adjusts itself to each patient's average blood pressure.

Interacciones potenciales de fármacos antihipertensivos en un año de estudio de pacientes con hipertensión arterial atendidos en hospitales de 11 municipios del Departamento de Risaralda-Colombia / Antihypertensive medicaments potential interactions in one year of study in hypertensive patients attended in hopitals from 11 country of the Risaralda Department-Colombia

En enfermedades como la hipertensión arterial con frecuencia deben utilizarse tratamientos con dos o más medicamentos, por lo cual el uso incorrecto de ellos puede conllevar a interacciones de fármacos. En el contexto de la hipertensión arterial en América Latina, existen escasos estudios evaluando la magnitud de este problema. Se realizó el presente estudio, observacional, transversal, con un muestreó censal, con el fin de establecer la ocurrencia de potenciales interacciones de fármacos en pacientes con hipertensión arterial de hospitales de 11 municipios de Risaralda, Colombia, agosto 2009 a agosto 2010, usando un algoritmo diseñado para identificar posibles interacciones de fármacos. Se obtuvieron 65.535 registros de prescripción de antihipertensivos, de 3.813 pacientes hipertensos, 28,46% correspondieron con hidroclorotiazida y 2007% enalapril, entre otros. Del total de pacientes 17,60% (IC95% 16,34%-18,82%) presentaron interacciones potenciales de fármacos, siendo la mayor en el municipio Dosquebradas (21,09%; IC95% 18,79%-23,36%). La interacción más frecuente fue enalapril-hidroclorotiazida (45,58% de los pacientes) y la de mayor riesgo y frecuencia fue enalapril-espironolactona (2,41%). estos resultados, reflejan en parte, falta de cumplimiento de normas de tratamiento de la hipertensión arterial, asi como poca implementación de conductas de tratamiento basadas en evidencia, y también posiblemente dificultades en la formación universitaria, falta de programas de educación médica continuada, falta de interés y tiempo para acceder a los alertas y reportes de nuevas condicones de uso de los medicamentos y poca instrucción y enseñanza de la medicina basada en evidencias, aspectos sobre los cuales se debe intervenir integralmente con distintos enfoques

In diseases such as hypertension, commonly treatments with two or more drugs should be used, then their incorrect use can lead to drug interactions. In the context of the hypertension in Latin America, there are few studies assessing the magnitude of this problem. Current, observational, cross-sectional and census study was made in order to establish the potential ocurrence of drug interactions in patients with hypertension from hospitals of 11 municipalities of Risaralba, Colombia, august 2009 to august 2010, using an algorithm designed to identify possible drug interactions. A total of 5.535 antihypertensive prescription records from 3.813 hypertension patients, 28.46% corresponding to hydrochlorothiazide and 20.07% to enalapril, among others, were obtained. From the total of patients 17.60% (95% CI 16.34 %-18.32%) presented potential drug interactions, being highest at the municipality Dosquebradas (21.09%; 95% CI 18.79%-23.36%). Most frequent interaction was enalapril-hydrochlorothiazide (45.58% of patients) and that of higher risk and frequency was enalapril-spironolactone (2.41%). These results, reflected in part, the lack of adherence to hypertension treatment guidelines, as well few implementation of evidenced based treatment conducts, and possibly too defficulties in the university formation, lack of continue medical education programs. Lack of interest and time to access to the alerts and reports of new conditions of drugs use and few instructions and teaching of evidence based medicine, aspects that needs tobe integrally intervened with different approaches

Estado del arte en la determinación de ácido úrico evluado frente a un método HPLC / State of the art determination of uric acid, evaluated front the HPLC method

Se utilizó un método HPLC de fase reversa para determinar el contenido de ácido úrico en 18 muestras de suficiencia (100 por ciento de suero equino) que fueron ensayadas durante 1993 y 1994 por los laboratorios clínicos participantes en el Programa Cubano de Control Externo de la Calidad. Los resultados reportados por los participantes se distribuyeron según el método químico empleado localmente en la determinación de ácido úrico (reducción del ácido fosfotúngstico, uricasa/manual, uricasa/automatizado) y se compararon con el valor obtenido por la aplicación HPLC. El intervalo permisible para la desviación respecto del valor-HPLC incluyó la mediana junto con 50 por ciento de los resultados obtenidos localmente con la reacción del ácido fosfotúngstico. El mayor número de valores aberrantes se asoció al uso del método colorimétrico. El paso a un método enzimático/automatizado significó una reducción de la frecuencia de aberrantes y un aumento marginal en el número de resultados satisfactorios. La versión manual de la reacción de la uricasa se caracterizó por su consistente desviación respecto del valor-HPLC. Se demuestran así las ventajas de la introducción de aplicaciones HPLC para analitos de química clínica, en un Programa de Control Externo, al disponer de una herramienta para identificar a los métodos químicos con pobre desempeño y segregarlos de aquéllos con un rendimiento superior.