Circulating Chemokines and Short- and Long-Term Outcomes After Ischemic Stroke.

Chemokines are vital in post-cerebral ischemia inflammatory reactions. We investigate the possible relationship between plasma chemokines and short-term and long-term outcomes after stroke. This study included 235 patients (median age, 72 years; 49.8% female) suffering from ischemic stroke, or transient ischemic attack admitted to the hospital within 24 h of onset. We evaluated chemokines CCL2, CCL5, CXCL8, CXCL9, and CXCL10 in plasma samples collected upon admission. Further, we assessed functional outcomes at 3- and 12-months, all-cause fatality over 5 years, and episodes of delirium within the first 7 days of admission. Multivariate analysis revealed an association between higher CXCL10 levels and an increased risk of poor functional outcomes at 3 months (OR: 3.02, 95%CI: 1.22-7.46, p = 0.016) and 12 months (OR: 2.32, 95%CI: 1.03-5.26, p = 0.043), as well as an increased death risk (HR: 1.79, 95%CI: 1.04-3.07, p = 0.036). High CXCL8 levels independently predicted poor functional outcomes at 12 months (OR: 2.69, 95%CI: 1.39-6.31, p = 0.005) and a higher 5-year case fatality rate (HR: 1.90, 95%CI: 1.23-2.93, p = 0.004). Elevated CXCL9 levels also predicted unfavourable functional outcomes at 12 months (OR: 2.45, 95%CI: 1.07-5.61, p = 0.034). In univariate analysis, increased levels of CXCL8, CXCL9, and CXCL10 showed an association with delirium, although this link was not evident in the multivariate analysis. Plasma CXCL8 and CXCL10 show potential as prognostic biomarkers for stroke outcomes and as therapeutic targets suitable for reverse translation.

Determinants of the Quality of Life in Patients with Drug-Resistant Temporal Lobe Epilepsy: A Comparison of the Results before and after Surgery.

Drug-resistant temporal lobe epilepsy is associated with a reduction in the quality of life of patients. The aim of this study was to compare the quality of life before and after the surgical treatment of epilepsy and to assess factors that may affect the well-being of patients after surgery. The study involved 168 patients with drug-resistant temporal lobe epilepsy. All of them were examined twice: once before and again one year after surgery. Two questionnaires were used in the study: the Quality of Life in Epilepsy Inventory-Patient-Weighted and Hospital Anxiety and Depression Scale and one that collected data on selected demographic and clinical variables. The results showed that patients scored significantly higher in quality of life and lower in depression and anxiety after surgery; however, this only applied to patients with a good outcome of treatment (Engel Class I and Class II). Patients with an unfavorable outcome of surgical treatment (Engel Class III and Class IV) achieved significantly worse results in all examined variables. Correlational analysis showed a relationship between select aspects of quality of life and the level of depression and anxiety, as well as the frequency of seizures and age at epilepsy onset. There was no significant relationship with age, sex, education, or number of prescribed antiepileptic drugs. The study confirms the significant relationship between the quality of life and the effectiveness of surgical treatment, indicating the relationship between patients' well-being and selected clinical indicators.

What helps patients to prepare for and cope during awake craniotomy? A prospective qualitative study.

There is growing interest in awake craniotomies, but some clinicians are concerned that such procedures are poorly tolerated by patients. Therefore, we conducted a study to assess this phenomenon. In this prospective qualitative study, 68 patients who qualified for awake craniotomy were asked to complete the Hospital Anxiety and Depression Scale (HADS)-two days before the surgery and visual analogue scales (VAS) for pain and stress, two days before the surgery and again about two days after. In addition, after their surgery, they took part in a structured interview about what helped them prepare for and cope with the surgery. Most patients tolerated the awake surgery well, scoring low on stress and pain scales. They reported a lower level of stress during the surgery (when questioned afterwards) than before it. Intensity of stress before the surgery correlated negatively with age, positively with HADS anxiety score and positively with stress subsequently experienced during surgery. The level of stress during surgery was associated with stress experienced before the surgery, pain and HADS anxiety and depression scores. Severity of pain during the surgery was positively correlated with stress during surgery and HADS depression and anxiety scores before the surgery. There was no correlation between stress, pain, anxiety and depression and the location of the lesion. Patients have a high tolerance for awake craniotomy. Various factors have an impact on how well patients cope with the operation. Extensive preoperative preparation should be considered a key part of the procedure.

Pre-stroke and early post-stroke apathy is associated with increased risk of dementia 3 months after stroke.

OBJECTIVES: Apathy is a frequent neuropsychiatric syndrome after stroke. We determined whether pre-morbid and early post-stroke apathy predicts dementia 3 months after stroke. METHODS: We included ischemic stroke patients without dementia who participated in the Prospective Observational Polish Study on post-stroke delirium. We used the Neuropsychiatric Inventory and clinician-reported version of Apathy Evaluation Scale to score apathy symptoms before stroke and on day 8 after stroke. Patients underwent neuropsychological examination 3 months after stroke. RESULTS: Of 422 patients with ischemic stroke and without pre-stroke dementia, 194 patients (mean age: 67.5 ± 12.3; 45.9% female) underwent neuropsychological examination. Dementia was diagnosed in 21.6% of them. Patients with dementia had higher apathy scores before stroke (mean: 0.9 ± 1.7 vs. 0.2 ± 0.9, p < 0.01) and on day 8 (mean: 37.2 ± 9.3 vs. 29.0 ± 9.6, p < 0.01). Depressive symptoms did not differ between groups. In multivariate analysis adjusted for age, diabetes mellitus, stroke severity and in-hospital delirium, apathy symptoms before stroke and on day 8 after stroke predicted post-stroke dementia (adjusted OR: 1.59, 95%CI: 1.13-2.26, p = 0.01 and OR: 1.06, 95%CI: 1.01-1.11, p = 0.03, respectively). CONCLUSIONS: Pre-stroke and early post-stroke apathy independently from age, stroke severity and delirium predicted dementia 3 months after stroke. Apathy might be useful in identifying at-risk patients.

Delayed symptomatic cerebral vasospasm after transsphenoidal resection of pituitary adenoma.

Not required for Clinical Vignette.

Reduced ex vivo TNFα synthesis upon whole blood stimulation with endotoxin predicts post-stroke fatigue.

OBJECTIVE: Fatigue is a common, debilitating syndrome after stroke. Peripheral inflammation plays a role in the pathogenesis of fatigue of different origin, but its contribution to post-stroke fatigue (PSF) remains unclear. We aimed to determine if there is any association between ex vivo synthesized and circulating cytokines, and risk of PSF. METHODS: We included 174 patients with ischemic stroke. We stimulated in vitro blood taken on day 3 after stroke with endotoxin. We measured ex vivo released (TNFα, IP-10, IL-1ß, IL-6, IL-8, IL-10, IL-12p70) and plasma (TNFα, IL-6, sIL-6R, IL-1Ra) cytokines. We assessed fatigue at month 3 using Fatigue Severity Scale (FSS). We used logistic regression to assess the relationship between cytokines and fatigue scores. RESULTS: Compared with patients with lower fatigue at month 3 (FSS < 36), patients with higher fatigue (FSS ≥ 36) had lower endotoxin-stimulated TNFα release after 24 h (median: 429 vs 581 pg/mL, P = 0.05). Plasma TNFα tended to be higher in patients who developed fatigue (median: 0.8 vs 0.6 pg/mL, P = 0.06). Other cytokines did not differ between groups. After adjusting for pre-stroke fatigue and depressive symptoms, TNFα release <559.7 pg/mL after 24 h was associated with an increased risk of PSF (OR: 2.61, 95%CI: 1.22-5.57, P = 0.01). Plasma TNFα >0.76 pg/mL was associated with higher risk of PSF in univariable (OR: 2.41, 95%CI: 1.13-5.15, P = 0.02), but not multivariable analysis (OR: 2.41, 95%CI: 0.96-6.00, P = 0.06). CONCLUSION: Reduced ex vivo TNFα synthesis upon whole blood stimulation with endotoxin in the acute phase of stroke predicted PSF.

Gene expression profiling in whole blood stimulated ex vivo with lipopolysaccharide as a tool to predict post-stroke depressive symptoms: Proof-of-concept study.

Prediction of post-stroke depressive symptoms (DSs) is challenging in patients without a history of depression. Gene expression profiling in blood cells may facilitate the search for biomarkers. The use of an ex vivo stimulus to the blood helps to reveal differences in gene profiles by reducing variation in gene expression. We conducted a proof-of-concept study to determine the usefulness of gene expression profiling in lipopolysaccharide (LPS)-stimulated blood for predicting post-stroke DS. Out of 262 enrolled patients with ischemic stroke, we included 96 patients without a pre-stroke history of depression and not taking any anti-depressive medication before or during the first 3 months after stroke. We assessed DS at 3 months after stroke using the Patient Health Questionnaire-9. We used RNA sequencing to determine the gene expression profile in LPS-stimulated blood samples taken on day 3 after stroke. We constructed a risk prediction model using a principal component analysis combined with logistic regression. We diagnosed post-stroke DS in 17.7% of patients. Expression of 510 genes differed between patients with and without DS. A model containing 6 genes (PKM, PRRC2C, NUP188, CHMP3, H2AC8, NOP10) displayed very good discriminatory properties (area under the curve: 0.95) with the sensitivity of 0.94 and specificity of 0.85. Our results suggest the potential utility of gene expression profiling in whole blood stimulated with LPS for predicting post-stroke DS. This method could be useful for searching biomarkers of post-stroke depression.

Subtemporal Approach and Its Infratentorial Extension: Review and a Comparative Analysis of Different Techniques.

Introduction Surgical resection of lesions occupying the incisural space is challenging. In a comparative fashion, we aimed to describe the anatomy and surgical approaches to the tentorial incisura and to the rostral brainstem via the intradural subtemporal approach and its infratentorial extensions. Methods Six fresh human head specimens (12 sides) were prepared for the microscopic dissection of the tentorial incisura using the intradural subtemporal approach and its infratentorial extensions. Endoscope was used to examine the anatomy of the region inadequately exposed with the microscope. Image-guided navigation was used to confirm bony structures visualized around the petrous apex. Results Standard subtemporal approach provides surgical access to the supratentorial brainstem above the pontomesencephalic sulcus and to the lateral surface of the cerebral peduncle. The linear or triangular tentorial divisions can provide access to the infratentorial space below the pontomesencephalic sulcus. The triangular tentorial flap in comparison with the linear incision obstructs the exposure of anterior incisural space and of the prepontine cistern. Visualization of the brainstem below the trigeminal nerve can be achieved by the anterior petrosectomy. Conclusion Infratentorial extension of the intradural subtemporal approach is technically demanding due to critical neurovascular structures and a relatively narrow corridor. In-depth anatomical knowledge is essential for the selection of the appropriate operative approach and safe surgical resections of lesions.

Monitored Anesthesia Care Protocol for Awake Craniotomy and Patient's Perspective on the Procedure.

OBJECTIVE: There is ongoing discussion on pros and cons in terms of different anesthesia protocols for awake craniotomy (AC) with direct brain stimulation. The aim of this study is to share our anesthesia protocol and present our patients' perspectives. METHODS: We conducted an analysis of prospectively collected data from 53 (54 procedures) consecutive patients. Most of the patients (50) underwent surgery due to primary brain lesions. Eight procedures were performed in patients with lesions in the nondominant hemisphere for language. Four of all procedures were reoperations, and one patient was operated on in awake conditions twice. The psychological evaluation of patients was performed 2 times: 2 days before and after surgery. A visual analog scale for pain and stress levels as well as structured interviews was used. RESULTS: Most patients tolerated ACwell. Patients reported that discomfort was mostly related to urinary catheter insertion, head holder placement, and temporal muscle detachment in cases of frontotemporal craniotomies. The intensity of stress measured with the visual analog scale before surgery was negatively associated with age and positively correlated with stress experienced in the operating room. In all patients, we were able to finish the procedure according to the monitored anesthesia care protocol without the need for conversion to general anesthesia. We observed 3 (5.6%) intraoperative seizures that required deepening of sedation. CONCLUSION: AC using the monitored anesthesia care protocol was a safe and well-tolerated procedure with satisfactory patient experience. Extensive preoperative preparation should be considered a key part of the procedure.

Serum C-reactive protein adds predictive information for post-stroke delirium: The PROPOLIS study.

OBJECTIVE: Delirium is common and serious complication after stroke. Accurate prediction of delirium is important for prevention and monitoring of high-risk patients. Our study aimed to determine if addition of C-reactive protein (CRP) to a model based on easy-to-access clinical predictors improves accuracy of delirium prediction in acute stroke patients. METHODS: We analyzed data of patients participating in the Prospective Observational Polish Study on post-stroke delirium. We included patients admitted within 24 h after stroke or transient ischemic attack (TIA) in whom serum CRP was measured on admission. We examined core features of delirium during first 7 days of hospitalization. We assessed if addition of CRP to two clinical models improved metrics of discrimination and reclassification. Model A included age and stroke severity and Model B included stroke severity, atrial fibrillation, diabetes mellitus, pre-stroke dependency, and hemorrhagic stroke. RESULTS: We included 459 patients. We diagnosed delirium in 29.2% of them. Patients who developed delirium had higher CRP level than those without delirium (median: 13.2 vs. 4.4 mg/L, p < 0.001). CRP >7.09 mg/L was associated with an increased risk of delirium (adjusted OR: 2.98, 95%CI: 1.71-5.19, p < 0.001). After adding CRP to clinical models, an area under receiver operator curve increased from 0.77 to 0.80 (p = 0.038) for Model A and from 0.81 to 0.84 (p = 0.016) for Model B. There was also improvement in reclassification. CONCLUSIONS: Addition of CRP to clinical predictors moderately improved prediction of post-stroke delirium. CRP could be considered as a potential biomarker to stratify risk of delirium after stroke.

Cortical and white matter anatomy relevant for the lateral and superior approaches to resect intraaxial lesions within the frontal lobe.

Despite being associated with high-order neurocognitive functions, the frontal lobe plays an important role in core neurological functions, such as motor and language functions. The aim of this study was to present a neurosurgical perspective of the cortical and subcortical anatomy of the frontal lobe in terms of surgical treatment of intraaxial frontal lobe lesions. We also discuss the results of direct brain mapping when awake craniotomy is performed. Ten adult cerebral hemispheres were prepared for white matter dissection according to the Klingler technique. Intraaxial frontal lobe lesions are approached with a superior or lateral trajectory during awake conditions. The highly eloquent cortex within the frontal lobe is identified within the inferior frontal gyrus (IFG) and precentral gyrus. The trajectory of the approach is mainly related to the position of the lesion in relation to the arcuate fascicle/superior longitudinal fascicle complex and ventricular system. Knowledge of the cortical and subcortical anatomy and its function within the frontal lobe is essential for preoperative planning and predicting the risk of immediate and long-term postoperative deficits. This allows surgeons to properly set the extent of the resection and type of approach during preoperative planning.

Attention and working memory in patients with prolactinomas: a case-control study.

Prolactinomas (prolactin-secreting adenomas) are the most common type of hormone-secreting pituitary tumor. Mounting evidence indicates that excess prolactin impairs cognitive function, but specific assessments of attention in patients with prolactinomas are lacking. Case-control study gathered 54 participants-27 patients with prolactinoma and 27 healthy controls. Neuropsychological assessment included a comprehensive set of diagnostic methods for the evaluation of attention and working memory. Patients showed slower information processing, expressed as a longer working time on the d2 Test of Attention and Color Trails Test (CTT-2), and lower attention-switching shown in the CTT-2 and in two subtests of the Tests of Everyday Attention (Visual Elevator), and Telephone Search While Counting. Working memory disturbances were observed in Digit Span and Symbol Span tests. A level of prolactin correlated negatively with scores in some of the neuropsychological tests measuring attentional switching (Visual Elevator), spatial screening and working memory (CTT-2), spatial working memory (Symbol Span) and auditory-verbal working memory (Digit Span backwards). There were no significant correlations between cognitive performance and tumor size. In conclusion, patients with prolactinoma suffer from impaired cognitive functions, including attention and working memory. Comprehensive neuropsychological assessment should be a permanent element of the diagnostics of this group of patients.

Long-Term Management of Seizures after Surgical Treatment of Supratentorial Cavernous Malformations : A Retrospective Single Centre Study.

OBJECTIVE: Seizure recurrence after the first-ever seizure in patients with a supratentorial cerebral cavernous malformation (CCM) is almost certain, so the diagnosis and treatment of epilepsy is justified. The optimal method of management of these patients is still a matter of debate. The aim of our study was to identify factors associated with postoperative seizure control and assess the surgical morbidity rate. METHODS: We retrospectively analysed 45 consecutive patients with a supratentorial CCM and symptomatic epilepsy in a single centre. Pre- and postoperative epidemiological data, seizure-related patient histories, neuroimaging results, surgery details and outcomes were obtained from hospital medical records. Seizure outcomes were assessed at least 12 months after surgery. RESULTS: Thirty-five patients (77.8%) were seizure free at the long-term follow-up (Engel class I); six (13,3%) had rare, nocturnal seizures (Engel class II); and four (8.9%) showed meaningful improvement (Engel class III). In 15 patients (33%) in the Engel I group; it was possible to discontinue antiepileptic medication. Although there was not statistical significance, our results suggest that patients can benefit from early surgery. No deaths occurred in our study, and mild postoperative neurologic deficits were observed in two patients (4%) at the long-term follow-up. CONCLUSION: Surgical resection of CCMs should be considered in all patients with a supratentorial malformation and epilepsy due to the favourable surgical results in terms of the epileptic seizure control rate and low postoperative morbidity risk, despite the use of different predictors for the seizure outcome.

The use of anticholinergic medication is associated with an increased risk of stroke-associated pneumonia.

BACKGROUND: Pneumonia is a frequent medical complication after stroke. A few studies showed that the use of anticholinergic medication is associated with a higher risk of community acquired pneumonia in the elderly. We aimed to determine if there is any association between anticholinergic medication used before stroke and stroke-associated pneumonia (SAP). METHODS: We analysed prospectively collected data of 675 patients with acute stroke (mean age 71.4 ± 13.3; 53.1% female). We used the Anticholinergic Drug Scale to assess anticholinergic exposure during a month preceding stroke onset. RESULTS: We diagnosed SAP in 14.7% of patients. The use of anticholinergic medication was associated with an elevated risk of SAP (OR 2.56, 95% CI 1.59-4.11, P < 0.01) in univariate analysis. This association remained significant in multivariable analysis adjusted for age, stroke severity, atrial fibrillation, previous myocardial infarction and respiratory tract diseases (OR 2.06, 95% CI 1.01-4.22, P = 0.04). CONCLUSIONS: The use of anticholinergic medication before stroke is associated with an increased risk of SAP.

Delirium and subsyndromal delirium are associated with the long-term risk of death after ischaemic stroke.

BACKGROUND: Post-stroke delirium has a negative impact on functional outcome. We explored if there is any association between delirium, subsyndromal delirium and long-term mortality after ischaemic stroke and transient ischaemic attack. METHODS: We included 564 patients with ischaemic stroke or transient ischaemic attack. We assessed symptoms of delirium during the first 7 days after admission. We used Cox proportional hazards models to analyse all-cause mortality during the first 5 years after stroke. RESULTS: We diagnosed delirium in 23.4% and subsyndromal delirium in 10.3% of patients. During the follow-up, 72.7% of patients with delirium, 51.7% of patients with subsyndromal delirium and 22.7% of patients without delirious symptoms died (P < 0.001). Patients with subsyndromal delirium and delirium had higher risk of death in the multivariate analysis (HR 1.72, 95% CI 1.11-2.68, P = 0.016 and HR 3.30, 95% CI 2.29-4.76, P < 0.001, respectively). CONCLUSIONS: Post-stroke delirium is associated with long-term mortality. Patients with subsyndromal delirium are at the intermediate risk of death.

Subtypes of delirium after ischaemic stroke-predisposing factors and outcomes: a prospective observational study (PROPOLIS).

BACKGROUND AND PURPOSE: Delirium is a serious complication after stroke. It remains unclear whether different motor subtypes of delirium are associated with diverse risk factors and outcomes. The aim was to investigate if delirium subtypes differ in predisposing factors, clinical characteristics and outcomes. METHODS: In all, 698 patients with ischaemic stroke or transient ischaemic attack (median age 73 years; 53.7% female) were prospectively included. Core features of delirium during the first 7 days after admission were examined. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for delirium were used. Pre-stroke characteristics were compared between different delirium subtypes and logistic regression and Cox proportional hazard models were used to explore the association between delirium, functional outcome and death. RESULTS: Hyperactive, hypoactive and mixed delirium were diagnosed in 28, 75 and 66 patients, respectively. Patients with hyperactive delirium had less severe neurological deficit on admission and more often had transient ischaemic attack compared with patients with hypoactive and mixed delirium. Compared with patients with hypoactive delirium, those with hyperactive delirium more often suffered from irritability/lability prior to stroke. Hyperactive and hypoactive delirium did not differ in age, sex, comorbidities, pre-stroke dependency, cognitive decline and severity of delirium. Hyperactive, hypoactive and mixed delirium were associated with an increased risk of poor 3- and 12-month functional outcome compared with patients without delirium. Moreover, patients with hypoactive and mixed delirium had an elevated risk of death. CONCLUSIONS: Hyperactive delirium is associated with less severe stroke and higher scores of pre-existing irritability/lability. All three motor subtypes of delirium are associated with poor outcome, although hyperactive delirium seems to have a less unfavourable prognosis.

Anatomical aspects of the insula, opercula and peri-insular white matter for a transcortical approach to insular glioma resection.

The insula is a lobe located deep in each hemisphere of the brain and is surrounded by eloquent cortical, white matter, and basal ganglia structures. The aim of this study was to provide an anatomical description of the insula and white matter tracts related to surgical treatment of gliomas through a transcortical approach. The study also discusses surgical implications in terms of intraoperative brain mapping. Five adult brains were prepared according to the Klingler technique. Cortical anatomy was evaluated with the naked eye, whereas white matter dissection was performed with the use of a microscope. The widest exposure of the insular surface was noted through the temporal operculum, mainly in zones III and IV according to the Berger-Sanai classification. By going through the pars triangularis in all cases, the anterior insular point and most of zone I were exposed. The narrowest and deepest operating field was observed by going through the parietal operculum. This method provided a suitable approach to zone II, where the corticospinal tract is not covered by the basal ganglia and is exposed just under the superior limiting sulcus. At the subcortical level, the identification of the inferior frontoocipital fasciculus at the level of the limen insulae is critical in terms of preserving the lenticulostriate arteries. Detailed knowledge of the anatomy of the insula and subcortical white matter that is exposed through each operculum is essential in preoperative planning as well as in the intraoperative decision-making process in terms of intraoperative brain mapping.