Exploring risk factors of severe pituitary apoplexy: Insights from a multicenter study of 71 cases.

PURPOSE: To identify clinical and radiological factors associated with a higher risk of developing a severe pituitary apoplexy (PA). METHODS: Multicenter retrospective study of patients presenting with clinical PA in three Spanish tertiary hospitals of Madrid between 2008 and 2022. We classified PA as severe when presenting with an altered level of consciousness (Glasgow Coma Scale (GCS) < 15) or visual involvement. RESULTS: A total of 71 PA cases were identified, of whom 80.28% (n = 57) were classified as severe PA. The median age was 60 (18 to 85 years old) and 67.6% (n = 48) were male. Most patients had macroadenomas, except for one patient with a microadenoma of 9 mm. Headache was the most common presenting symptom (90.1%) and anticoagulation was the most frequent predisposing risk factor, but it was not associated with a higher risk for severe PA (odds ratio [OR] 1.13 [0.21-5.90]). Severe cases were associated with male gender (OR 5.53 [1.59-19.27]), tumor size >20 mm (OR 17.67 [4.07-76.64]), and Knosp grade ≥2 (OR 9.6 [2.38-38.73]). In the multivariant analysis, the only variables associated with a higher risk for severe PA were tumor size and Knosp grade. Surgery was more common in severe PA than in non-severe (91.2% vs. 64.3%, P = 0.009). CONCLUSION: A tumor size >20 mm and cavernous sinus invasion are risk factors for developing a severe PA. These risk factors can stratify patients at a higher risk of a worse clinical picture, and subsequently, more need of decompressive surgery.

Performance of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) biomarkers in predicting CT scan results and neurological outcomes in children with traumatic brain injury (BRAINI-2 paediatric study): protocol of a European prospective multicentre study.

INTRODUCTION: In light of the burden of traumatic brain injury (TBI) in children and the excessive number of unnecessary CT scans still being performed, new strategies are needed to limit their use while minimising the risk of delayed diagnosis of intracranial lesions (ICLs). Identifying children at higher risk of poor outcomes would enable them to be better monitored. The use of the blood-based brain biomarkers glial fibrillar acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) could help clinicians in this decision. The overall aim of this study is to provide new knowledge regarding GFAP and UCH-L1 in order to improve TBI management in the paediatric population. METHODS AND ANALYSIS: We will conduct a European, prospective, multicentre study, the BRAINI-2 paediatric study, in 20 centres in France, Spain and Switzerland with an inclusion period of 30 months for a total of 2880 children and adolescents included. To assess the performance of GFAP and UCH-L1 used separately and in combination to predict ICLs on CT scans (primary objective), 630 children less than 18 years of age with mild TBI, defined by a Glasgow Coma Scale score of 13-15 and with a CT scan will be recruited. To evaluate the potential of GFAP and UCH-L1 in predicting the prognosis after TBI (secondary objective), a further 1720 children with mild TBI but no CT scan as well as 130 children with moderate or severe TBI will be recruited. Finally, to establish age-specific reference values for GFAP and UCH-L1 (secondary objective), we will include 400 children and adolescents with no history of TBI. ETHICS AND DISSEMINATION: This study has received ethics approval in all participating countries. Results from our study will be disseminated in international peer-reviewed journals. All procedures were developed in order to assure data protection and confidentiality. TRIAL REGISTRATION NUMBER: NCT05413499.

ApTOLL: A new therapeutic aptamer for cytoprotection and (re)myelination after multiple sclerosis.

BACKGROUND AND PURPOSE: ApTOLL is an aptamer selected to antagonize toll-like receptor 4 (TLR4), a relevant actor for innate immunity involved in inflammatory responses in multiple sclerosis (MS) and other diseases. The currently available therapeutic arsenal to treat MS is composed of immunomodulators but, to date, there are no (re)myelinating drugs available in clinics. In our present study, we studied the effect of ApTOLL on different animal models of MS. EXPERIMENTAL APPROACH: The experimental autoimmune encephalomyelitis (EAE) model was used to evaluate the effect of ApTOLL on reducing the inflammatory component. A more direct effect on oligodendroglia was studied with the cuprizone model and purified primary cultures of murine and human oligodendrocyte precursor cells (OPCs) isolated through magnetic-activated cell sorting (MACS) from samples of brain cortex. Also, we tested these effects in an ex vivo model of organotypic cultures demyelinated with lysolecithin (LPC). KEY RESULTS: ApTOLL treatment positively impacted the clinical symptomatology of mice in the EAE and cuprizone models, which was associated with better preservation plus restoration of myelin and oligodendrocytes in the demyelinated lesions of animals. Restoration was corroborated on purified cultures of rodent and human OPCs. CONCLUSION AND IMPLICATIONS: Our findings reveal a new therapeutic approach for the treatment of inflammatory and demyelinating diseases such as MS. The molecular nature of the aptamer exerts not only an anti-inflammatory effect but also neuroprotective and remyelinating effects. The excellent safety profile demonstrated by ApTOLL in animals and humans opens the door to future clinical trials in MS patients.

Twelve controversial questions in aneurysmal subarachnoid hemorrhage / Doce preguntas controvertidas en hemorragia subaracnoidea aneursmática

Critical care management of aneurysmal subarachnoid hemorrhage (aSAH) remains a major challenge. Despite the recent publication of guidelines from the American Heart Association/American Stroke Association and the Neurocritical Care Society, there are many controversial questions in the intensive care unit (ICU) management of this population. The authors provide an analysis of common issues in the ICU and provide guidance on the daily management of this specific population of neurocritical care patients. (AU)

El manejo en la unidad de cuidados intensivos (UCI) de los pacientes con hemorragia subaracnoidea aneurismática continua siendo un reto. A pesar de la publicación de las guías de la American Heart Association/American Stroke Association y la Neurocritical Care Society todavía existen muchos aspectos controvertidos en el manejo de esta población en la UCI. Los autores proporcionan un detenido análisis de los problemas habituales en la UCI y proporcionan recomendaciones en el manejo diario de esta población específica de pacientes neurocríticos. (AU)

Early management of adult traumatic spinal cord injury in patients with polytrauma: a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS).

BACKGROUND: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies. METHODS: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted. RESULTS: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak). CONCLUSIONS: This consensus provides practical recommendations to support a clinician's decision making in the management of tSCI polytrauma patients.

Impact of a Hospitalist Co-Management Program on Medical Complications and Length of Stay in Neurosurgical Patients.

BACKGROUND: The impact of co-management on clinical outcomes in neurosurgical patients is uncertain. This study aims to describe the implementation of a hospitalist co-management program in a neurosurgery department and its impact on the incidence of complications, mortality, and length of stay. METHODS: The authors used a quasi-experimental study design that compared a historical control period (July-December 2017) to a prospective intervention arm. During the intervention period, patients admitted to a neurosurgery inpatient unit who were older than 65 years, suffered certain conditions, or were admitted from ICUs were included in the co-management program. Two hospitalists joined the surgical staff and intervened in the diagnostic and therapeutical plan of patients, participating in clinical decisions and coordinating patient navigation with neurosurgeons. The incidence of moderate or severe complications measured by the Accordion Severity Grading System, in-hospital mortality, and length of stay of the two cohorts were compared. Multivariate regression was used to adjust for confounders, and the average treatment effect was estimated using inverse probability of treatment weighting. RESULTS: The adjusted incidence of moderate or severe complications was lower among co-managed patients (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.39-0.91). Mortality was unchanged (OR 0.83, 95% CI 0.15-4.17). Length of stay was lower in co-managed patients, with a 1.3-day reduction observed after inverse probability of treatment weighting analysis. CONCLUSION: Hospitalist co-management was associated with a reduced incidence of complications and length of stay in neurosurgical patients, but there was no difference in in-hospital mortality.

Twelve controversial questions in aneurysmal subarachnoid hemorrhage.

Critical care management of aneurysmal subarachnoid hemorrhage (aSAH) remains a major challenge. Despite the recent publication of guidelines from the American Heart Association/American Stroke Association and the Neurocritical Care Society, there are many controversial questions in the intensive care unit (ICU) management of this population. The authors provide an analysis of common issues in the ICU and provide guidance on the daily management of this specific population of neurocritical care patients.

Pericytes and vascular smooth muscle cells in central nervous system arteriovenous malformations.

Previously considered passive support cells, mural cells-pericytes and vascular smooth muscle cells-have started to garner more attention in disease research, as more subclassifications, based on morphology, gene expression, and function, have been discovered. Central nervous system (CNS) arteriovenous malformations (AVMs) represent a neurovascular disorder in which mural cells have been shown to be affected, both in animal models and in human patients. To study consequences to mural cells in the context of AVMs, various animal models have been developed to mimic and predict human AVM pathologies. A key takeaway from recently published work is that AVMs and mural cells are heterogeneous in their molecular, cellular, and functional characteristics. In this review, we summarize the observed perturbations to mural cells in human CNS AVM samples and CNS AVM animal models, and we discuss various potential mechanisms relating mural cell pathologies to AVMs.

Study protocol for investigating the clinical performance of an automated blood test for glial fibrillary acidic protein and ubiquitin carboxy-terminal hydrolase L1 blood concentrations in elderly patients with mild traumatic BRAIN Injury and reference values (BRAINI-2 Elderly European study): a prospective multicentre observational study.

INTRODUCTION: Two blood brain-derived biomarkers, glial fibrillar acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), can rule out intracranial lesions in patients with mild traumatic brain injury (mTBI) when assessed within the first 12 hours. Most elderly patients were excluded from previous studies due to comorbidities. Biomarker use in elderly population could be affected by increased basal levels. This study will assess the performance of an automated test for measuring serum GFAP and UCH-L1 in elderly patients to predict the absence of intracranial lesions on head CT scans after mTBI, and determine both biomarkers reference values in a non-TBI elderly population. METHODS AND ANALYSIS: This is a prospective multicentre observational study on elderly patients (≥65 years) that will be performed in Spain, France and Germany. Two patient groups will be included in two independent substudies. (1) A cohort of 2370 elderly patients (1185<80 years and 1185≥80 years; BRAINI2-ELDERLY DIAGNOSTIC AND PROGNOSTIC STUDY) with mTBI and a brain CT scan that will undergo blood sampling within 12 hours after mTBI. The primary outcome measure is the diagnostic performance of GFAP and UCH-L1 measured using an automated assay for discriminating between patients with positive and negative findings on brain CT scans. Secondary outcome measures include the performance of both biomarkers in predicting early (1 week) and midterm (3 months) neurological status and quality of life after trauma. (2) A cohort of 480 elderly reference participants (BRAINI2-ELDERLY REFERENCE STUDY) in whom reference values for GFAP and UCHL1 will be determined. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Institutional Review Boards of Hospital 12 de Octubre in Spain (Re#22/027) and Southeast VI (Clermont Ferrand Hospital) (Re# 22.01782.000095) in France. The study's results will be presented at scientific meetings and published in peer-review publications. TRIAL REGISTRATION NUMBER: NCT05425251.

Differences in clinical, hormonal, and radiological presentation and in surgical outcomes in patients presenting with and without pituitary apoplexy. A multicenter study of 245 cases.

PURPOSE: To compare the clinical, hormonal, and radiological presentation and surgical outcomes of patients with macroadenomas presenting with pituitary apoplexy and patients not presenting pituitary apoplexy. METHODS: Multicentre retrospective study of patients presenting with macroadenomas and pituitary apoplexy in three Spanish tertiary hospitals between 2008 and 2022. We selected as control group (non-pituitary apoplexy), patients with pituitary macroadenomas without apoplexy who underwent pituitary surgery between 2008 and 2020. RESULTS: A total of 60 patients with apoplexy and 185 without apoplexy were enrolled. Patients with pituitary apoplexy were more frequently men (70% vs. 48.1%, p = 0.003), had higher prevalence of hypertension (43.3% vs. 26.0%, p = 0.011) and of obesity (23.3% vs. 9.7%, P = 0.007), were under treatment with anticoagulants more commonly (11.7% vs. 4.3%, P = 0.039) and had larger (27.5 ± 11.03 vs. 23.6 ± 12.55 mm, p = 0.035) and invasive pituitary macroadenomas more frequently (85.7% vs. 44.3%, P < 0.001) than those without apoplexy. Surgical remission was more frequent in patients with pituitary apoplexy than those without apoplexy (OR 4.55, P < 0.001), but they developed new pituitary deficits (OR 13.29, P < 0.001) and permanent diabetes insipidus (OR 3.40, P = 0.022) more commonly. However, visual improvement (OR 6.52, p < 0.001) and complete pituitary function recovery (OR 2.37, P < 0.001) was more common in patients without apoplexy. CONCLUSION: Surgical resection is more common in patients presenting with pituitary apoplexy than those without apoplexy; however, visual improvement and complete recovery of pituitary function is more common in patients without apoplexy. The risk of new pituitary deficits and permanent diabetes insipidus is higher in patients with apoplexy than in those without it.

Atlanto-occipital dislocation with concomitant severe traumatic brain injury: A retrospective study at a level 1 trauma center / Luxación atlantooccipital con traumatismo craneoencefálico grave concomitante: estudio retrospectivo en un centro de trauma de nivel 1

Background: Traumatic atlanto-occipital dislocation (AOD) is a life-threatening injury. Although traumatic brain injury (TBI) is associated with increased mortality in AOD patients, a detailed individual analysis of these patients is lacking in the literature. Methods: Patients ≥16 years old who were diagnosed of AOD with concomitant severe TBI from 2010 to 2020 were included in this retrospective study. We examined the epidemiology, injury mechanisms, associated injuries, and outcomes of these patients. Results: Eight patients were included. Six patients died before any intervention could be performed, and two patients underwent an occipito-cervical fixation, showing a notorious neurologic improvement on follow-up. Cardiorespiratory arrest (CRA) was a strong predictor of subsequent death. CT signs of diffuse axonal injury (DAI) were present in most patients and were confirmed by magnetic resonance imaging (MRI) in survivors. Although TBI was not the main cause of death, it was responsible for the delayed neurological improvement and deferred stabilization. The average sensitivity of the different used methodologies for AOD diagnosis ranged from 0.50 to 1.00, being the Basion Dens Interval (BDI) and the Condyle-C1 interval (CCI) sum the most reliable criteria. Non-survivors tended to show greater distraction measurements. The high incidence of condylar avulsion fractures suggests that their visualization on the initial CT study should heighten the suspicion for AOD. Conclusions: Our data suggest that patients with AOD and concomitant severe TBI might be salvageable patients. In those who survive beyond the first hospital days and show neurological improvement, surgical treatment should be performed as they can achieve an important neurologic recovery. (AU)

Antecedentes: La luxación atlantooccipital (AOD) traumática es una lesión potencialmente mortal. Aunque el traumatismo craneoencefálico (TCE) se asocia con un aumento de la mortalidad en los pacientes con AOD, no existe en la literatura un análisis individual detallado de estos pacientes. Métodos: En este estudio retrospectivo se incluyeron pacientes mayores de 16 años que fueron diagnosticados de AOD con TCE grave concomitante durante el periodo 2010-2020. Estudiamos la epidemiología, los mecanismos lesionales, así como las lesiones asociadas y los resultados de estos pacientes. Resultados: Se incluyeron ocho pacientes. Seis pacientes fallecieron antes de que se pudiera realizar cualquier intervención y dos pacientes fueron sometidos a una fijación occipitocervical, mostrando una notoria mejoría neurológica durante el seguimiento. La parada cardiorrespiratoria fue un predictor de muerte. En la TC inicial, signos de lesión axonal difusa estaban presentes en la mayoría de los pacientes y se confirmaron mediante imágenes de resonancia magnética en los supervivientes. Aunque el TCE no fue la principal causa de muerte, fue responsable de una mejoría neurológica tardía y por ello una estabilización diferida. La sensibilidad de las diferentes metodologías utilizadas para el diagnóstico de AOD osciló entre 0,50 y 1,00, siendo el intervalo Basion Dens y la suma del intervalo Condylo-C1 los criterios más fiables. Además, los no supervivientes presentaban mayores medidas de distracción. La alta incidencia de fracturas de cóndilo por avulsión sugiere que su visualización en el estudio de TC inicial debería aumentar la sospecha de AOD. Conclusiones: Nuestros datos sugieren que los pacientes con AOD y TCE grave concomitante podrían ser pacientes salvables. En aquellos que sobreviven más allá de los primeros días de...(AU)Palabras clave:Luxación atlantooccipitalColumna cervicalUnión craneocervicalFusión occipitocervicalTraumatismo craneoencefálico

Atlanto-occipital dislocation with concomitant severe traumatic brain injury: A retrospective study at a level 1 trauma center.

BACKGROUND: Traumatic atlanto-occipital dislocation (AOD) is a life-threatening injury. Although traumatic brain injury (TBI) is associated with increased mortality in AOD patients, a detailed individual analysis of these patients is lacking in the literature. METHODS: Patients ≥16 years old who were diagnosed of AOD with concomitant severe TBI from 2010 to 2020 were included in this retrospective study. We examined the epidemiology, injury mechanisms, associated injuries, and outcomes of these patients. RESULTS: Eight patients were included. Six patients died before any intervention could be performed, and two patients underwent an occipito-cervical fixation, showing a notorious neurologic improvement on follow-up. Cardiorespiratory arrest (CRA) was a strong predictor of subsequent death. CT signs of diffuse axonal injury (DAI) were present in most patients and were confirmed by magnetic resonance imaging (MRI) in survivors. Although TBI was not the main cause of death, it was responsible for the delayed neurological improvement and deferred stabilization. The average sensitivity of the different used methodologies for AOD diagnosis ranged from 0.50 to 1.00, being the Basion Dens Interval (BDI) and the Condyle-C1 interval (CCI) sum the most reliable criteria. Non-survivors tended to show greater distraction measurements. The high incidence of condylar avulsion fractures suggests that their visualization on the initial CT study should heighten the suspicion for AOD. CONCLUSIONS: Our data suggest that patients with AOD and concomitant severe TBI might be salvageable patients. In those who survive beyond the first hospital days and show neurological improvement, surgical treatment should be performed as they can achieve an important neurologic recovery.

Novel CT-based parameters assessing relative cross-sectional area to guide surgical management and predict clinical outcomes in patients with acute subdural hematoma.

INTRODUCTION: Acute subdural hematoma (aSDH) is one of the most devastating entities secondary to traumatic brain injury (TBI). Even though radiological computed tomography (CT) findings, such as hematoma thickness (HT), midline shift (MLS), and MLS/HT ratio, have an important prognostic role, they suffer from important drawbacks. We hypothesized that relative cross-sectional area (rCSA) of specific brain regions would provide valuable information about brain compression and swelling, thus being a key determining factor governing the clinical course. METHODS: We performed an 8-year retrospective analysis of patients with moderate to severe TBI with surgically evacuated, isolated, unilateral aSDH. We investigated the influence of aSDH rCSA and ipsilateral hemisphere rCSA along the supratentorial region on the subsequent operative technique employed for aSDH evacuation and patient's clinical outcomes (early death and Glasgow Outcome Scale [GOS] at discharge and after 1-year follow-up). Different conventional radiological variables were also assessed. RESULTS: The study included 39 patients. Lower HT, MLS, hematoma volume, and aSDH rCSA showed a significant association with decompressive craniectomy (DC) procedure. Conversely, higher ipsilateral hemisphere rCSA along the dorso-ventral axis and, specifically, ipsilateral hemisphere rCSA at the high convexity level were predictors for DC. CT segmentation analysis exhibited a modest relationship with early death, which was limited to the basal supratentorial subregion, but could not predict long-term outcome. CONCLUSION: rCSA is an objectifiable and reliable radiologic parameter available on admission CT that might provide valuable information to optimize surgical treatment.

Serum assessment of traumatic axonal injury: the correlation of GFAP, t-Tau, UCH-L1, and NfL levels with diffusion tensor imaging metrics and its prognosis utility.

OBJECTIVE: Diagnosis of traumatic axonal injury (TAI) is challenging because of its underestimation by conventional MRI and the technical requirements associated with the processing of diffusion tensor imaging (DTI). Serum biomarkers seem to be able to identify patients with abnormal CT scanning findings, but their potential role to assess TAI has seldomly been explored. METHODS: Patients with all severities of traumatic brain injury (TBI) were prospectively included in this study between 2016 and 2021. They underwent blood extraction within 24 hours after injury and imaging assessment, including DTI. Serum concentrations of glial fibrillary acidic protein, total microtubule-associated protein (t-Tau), ubiquitin C-terminal hydrolase L1 (UCH-L1), and neurofilament light chain (NfL) were measured using an ultrasensitive Simoa multiplex assay panel, a digital form of enzyme-linked immunosorbent assay. The Glasgow Outcome Scale-Extended score was determined at 6 months after TBI. The relationships between biomarker concentrations, volumetric analysis of corpus callosum (CC) lesions, and fractional anisotropy (FA) were analyzed by nonparametric tests. The prognostic utility of the biomarker was determined by calculating the C-statistic and an ordinal regression analysis. RESULTS: A total of 87 patients were included. Concentrations of all biomarkers were significantly higher for patients compared with controls. Although the concentration of the biomarkers was affected by the presence of mass lesions, FA of the CC was an independent factor influencing levels of UCH-L1 and NfL, which positioned these two biomarkers as better surrogates of TAI. Biomarkers also performed well in determining patients who would have had unfavorable outcome. NfL and the FA of the CC are independent complementary factors related to outcome. CONCLUSIONS: UCH-L1 and NfL seem to be the biomarkers more specific to detect TAI. The concentration of NfL combined with the FA of the CC might help predict long-term outcome.

Variability in the indication of brain CT scan after mild traumatic brain injury. A transnational survey.

PURPOSE: Clinical guidelines have been developed to standardize the management of mild traumatic brain injury (mTBI) in the emergency room, in particular the indication of brain CT scan and the use of blood biomarkers. The objective of this study was to determine the degree of adherence to guidelines in the management of these patients across four countries of Southern Europe. METHODS: An electronic survey including structural and general management of mTBI patients and six clinical vignettes was conducted. In-charge physicians from France, Spain, Greece and Portugal were contacted by telephone and email. Differences among countries were searched using an unconditional approach test on contingency tables. RESULTS: One hundred and eighty eight physicians from 131 Hospitals (78 Spain, 36 France, 12 Greece and 5 Portugal) completed the questionnaire. There were differences regarding the in-charge specialist across these countries. There was variability in the use of guidelines and their adherence. Spain was the country with the least guideline adherence. There was a global agreement in ordering a brain CT for patients receiving anticoagulation or platelet inhibitors, and for patients with seizures, altered consciousness, neurological deficit, clinical signs of skull fracture or signs of facial fracture. Aging was not an indication for CT in French centres. Loss of consciousness and posttraumatic amnesia were considered as indications for CT more frequently in Spain than in France. These findings were in line with the data from the 6 clinical vignettes. The estimated use of CT reached around 50% of mTBI cases. The use of S100B is restricted to five French centres. CONCLUSIONS: There were large variations in the guideline adherence, especially in the situations considered to order brain CT after mTBI.

Task synergies in neurovascular surgery: Image-guided navigation using a thermoplastic facial mask for the resection of a symptomatic occult to MRI brain microarteriovenous malformation.

Due to the size of microarteriovenous malformations (mAVM), its precise angioarchitecture description often requires a supraselective DSA and detecting the nidus during microsurgical resection is challenging. An accurate intraoperative navigation system is desirable but available softwares which can combine DSA and MRI are not always available. The authors present here a technical note describing the use of a stereotactic thermoplastic mask with a fiducial box to guide the resection of a mAVM.

Surgery for acute subdural hematoma: the value of pre-emptive decompressive craniectomy by propensity score analysis.

BACKGROUND: Acute subdural hematomas (ASDH) are found frequently following traumatic brain injury (TBI) and they are considered the most lethal type of mass lesions. The decision to perform a procedure to evacuate ASDH and the approach, either via craniotomy or decompressive craniectomy (DC), remains controversial. METHODS: We reviewed a prospectively collected series of 343 moderate to severe TBI patients in whom ASDH was the main lesion (ASDH volumes ≥10 cc). Patients with early comfort measures (early mortality prediction >50% and not ICP monitored), bilateral ASDH or the presence of another intracranial hematoma with volumes exceeding two times the volume of the ASDH were excluded. Among them, 112 were managed conservatively, 65 underwent ASDH evacuation by craniotomy and 166 by DC (103 pre-emptive DC, 63 obligatory DC). We calculated the average treatment effect by propensity score (PS) analysis using the following covariates: age, year, hypoxia, shock, pupils, major extracranial injury, motor score, midline shift, ASDH volume, swelling, intraventricular and subarachnoid hemorrhage presence. Then, multivariable binary regression and ordinal logistic regression analysis were performed to estimate associations between predictors and mortality and 12 months-GOS respectively. The patients' inverse probability weights were included as an independent variable in both regression models. RESULTS: The main variables associated with outcome were year, age, falls from patient´s own height, hypoxia, early deterioration, pupillary abnormalities, basal cistern effacement, compliance to ICP monitoring guidelines and type of surgical approach (craniotomy and pre-emptive DC). CONCLUSIONS: According to sliding dichotomy analysis, we found that patients in the intermediate or worst bands of unfavorable outcome prognosis seemed to achieve better than expected outcome if they underwent pre-emptive DC rather than craniotomy.

Effects of cranioplasty in cerebral blood perfusion using quantification with 99m-Tc HMPAO SPECT-CT.

BACKGROUND AND PURPOSE: Syndrome of the trephined or sinking skin flap syndrome is an underdiagnosed condition of craniectomized patients that usually improves after cranioplasty. Among the pathophysiological theories proposed, the changes of cerebral blood perfusion (CBP) caused by cranial defects might have a role in the neurological deficiencies observed. We aim to assess the regional cortex changes in CBP after cranioplasty with Technetium 99m hexamethylpropylene-amine oxime (99mTc-HMPAO) SPECT-CT. METHODS: Twenty-eight craniectomized patients subject to cranioplasty were studied with 99mTc-HMPAO SPECT-CT in three different times, before cranioplasty, a week, and 3 months after. The images were processed with quantification software comparing CBP of 24 cortical areas with a reference area, and with a database of controls. A mixed effects model and T-Student were used. RESULTS: CBP increased significantly in both hemispheres after cranioplasty, either using ratio (ß = .019, p-value = .030 first postsurgical SPECT-CT and ß = .021, p-value = .015 in the second study, vs. presurgical) or Z-score (ß = .220, p-value = .026 and ß = .279, p-value = .005, respectively). Nine areas of the damaged side had a significant lower CBP ratio and Z-score than the undamaged. Posterior cingulate showed an increased CBP ratio (p-value = .034) and Z-score (p-value = .028) in the first postsurgical SPECT-CT. These posterior cingulate changes represent a 4.83% increase in ratio and 91.04% in Z-Score (p-value = .035 and .040, respectively). CONCLUSION: CBP changes significantly in specific cortical areas after cranioplasty. Posterior cingulate changes might explain some improvements in attention impairments. SPECT-CT could be a useful tool to assess CBP changes in these patients and might be helpful in their clinical management.

Efficacy of percutaneous pedicle screws for thoracic and lumbar spine fractures compared with open technique.

BACKGROUND: The objective of this study is to compare percutaneous techniques (MIS) with the open technique in terms of angle correction, long-term maintenance and clinical results. METHODS: The authors collected a prospective database of thoraco-lumbar fractures treated with posterior stabilization without fusion from 2013 to 2019. The statistical analysis has been carried out retrospectively. The patients were classified into Open and MIS group. To compare the two population, samples, treatments and mitigate the differences between the groups, the propensity score (PS) matching was used. RESULTS: One hundred and eight patients with thoraco-lumbar fractures were included. After performing the PS, 21 patients were obtained in the open group and 28 in the MIS group. For operative and perioperative parameters there were no differences in number of patients with posterior decompression, number of instrumented segments, number of total screws, operative time and complications. Postoperative hemoglobin was similar in both groups. However, in the open group a greater loss of hemoglobin was observed; as well as, higher analgesia requirements and length of stay. No statistically significant differences were observed in neurological status in both groups in the preoperative, postoperative period and at follow-up. The Cobb angle showed no differences at admission comparing both groups. A similar angle correction was observed with both surgeries, but in open surgery there was a statistically significant loss of correction. CONCLUSIONS: We observed in this study that the MIS technique for the treatment of thoracolumbar fractures is as effective as the open technique in terms of angle correction; and demonstrated that is better in its maintenance over time. Clinical results were at least as good as with the open technique.

Extensive pharmacokinetic variability of Levetiracetam. ¿Are doctors aware?

INTRODUCTION: Levetiracetam was presented as a drug with linear pharmacokinetics. There is currently evidence on its extensive pharmacokinetic variability in real clinical practice. OBJECTIVE: To describe levetiracetam pharmacokinetic variability in patients with epilepsy in real clinical practice. To evaluate the effect on levetiracetam levels of gender, age, renal function, and polytherapy. To describe how clinicians prescribe based on age and co-medication. METHODS: Retrospective analysis of epilepsy patients treated with levetiracetam for whom plasma levels were available. RESULTS: 151 patients. Median levetiracetam level of 17.75 mg/L, median dose of 2000 mg/day. There was a significant correlation between daily dose and serum levels (p < 0.01). There was a 18.1% increase in levetiracetam concentration/dose ratio in patients over 65 years of age (p < 0.05) that also correlated with decreased glomerular filtration (p < 0.01). Clinicians corrected doses so patients over 65 years had similar levels than younger patients. There was a 30.1% decrease of concentration/dose ratio in patients on polytherapy with potent enzyme inducer antiseizure medication (p < 0.05), and a 46.3% decrease for carbamazepine (p < 0.01). Clinicians did not correct doses, so patients treated with levetiracetam and carbamazepine had 27.5% lower levels than patients taking other polytherapy. CONCLUSION: The pharmacokinetic variability of levetiracetam is wider than originally thought. Age and co-medication with strong enzyme-inducing drugs, especially carbamazepine, significantly influence levetiracetam levels. Clinicians at our center did not consider this interaction and prescribed similar doses of levetiracetam when it was used in combination with these drugs or with others, so they probably were not aware of this interaction.