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BACKGROUND AND AIMS: To investigate the prognostic value of blood neurofilament light chain protein (NfL) levels in the acute phase of coronavirus disease 2019 (COVID-19).

METHODS: We conducted an individual participant data (IPD) meta-analysis after screening on MEDLINE and Scopus to May 23rd 2022. We included studies with hospitalized adult COVID-19 patients without major COVID-19-associated central nervous system (CNS) manifestations and with a measurement of blood NfL in the acute phase as well as data regarding at least one clinical outcome including intensive care unit (ICU) admission, need of mechanical ventilation (MV) and death. We derived the age-adjusted measures NfL Z scores and conducted mixed-effects modelling to test associations between NfL Z scores and other variables, encompassing clinical outcomes. Summary receiver operating characteristic curves (SROCs) were used to calculate the area under the curve (AUC) for blood NfL.

RESULTS: We identified 382 records, of which 7 studies were included with a total of 669 hospitalized COVID-19 cases (mean age 66.2 ± 15.0 years, 68.1% males). Median NfL Z score at admission was elevated compared to the age-corrected reference population (2.37, IQR: 1.13-3.06, referring to 99th percentile in healthy controls). NfL Z scores were significantly associated with disease duration and severity. Higher NfL Z scores were associated with a higher likelihood of ICU admission, need of MV, and death. SROCs revealed AUCs of 0.74, 0.80 and 0.71 for mortality, need of MV and ICU admission, respectively.

CONCLUSIONS: Blood NfL levels were elevated in the acute phase of COVID-19 patients without major CNS manifestations and associated with clinical severity and poor outcome. The marker might ameliorate the performance of prognostic multivariable algorithms in COVID-19.

Objective

To study associations of clinical characteristics and treatment choice with functional outcome, mortality, and time to death in a national sample of aneurysmal subarachnoidal hemorrhage patients.

Methods

Data were extracted from a prospective nationwide multicenter study performed in September 2014 to March 2018. Glasgow Outcome Scale Extended (GOSE) grade, 1-year mortality, and survival probability were assessed at one year after ictus. Logistic univariate, multivariate, and Cox regression analyses were used to study the variables' associations with the outcomes.

Results

Unfavorable dichotomized GOSE (dGOSE; grades 1–4) was observed in 35.4% of patients. Microsurgery was preferred for middle cerebral artery aneurysms and Fisher grade 4. Treatment modality was not associated with any outcome measure. Dichotomized World Federation of Neurosurgical Societies (dWFNS), age, and delayed ischemic neurological deficit (DIND) showed significant correlations with dGOSE and 1-year mortality in multivariate regression analyses. Pupil dilatation was associated with a 1-year mortality outcome. Cox regression analysis showed lower survival probability for pupil dilatation (hazard ratio [HR]: 3.546), poor dWFNS (HR: 3.688), higher age (HR: 1.051), and DIND occurrence (HR: 2.214).

Conclusions

The patient selection in Sweden after aneurysmal subarachnoidal hemorrhage showed similar values for dGOSE, 1-year mortality, and survival probability between patients treated with microsurgery or endovascular technique. Poor dWFNS, higher age, and DIND were significantly associated with unfavorable dGOSE, mortality, and survival probability. Pupil dilatation was significantly associated with mortality and survival probability.

OBJECTIVE: A small posterior fossa (PF) has been hypothesized to explain the increased incidence of trigeminal neuralgia (TN) in females and could make microvascular decompression (MVD) more challenging. The aim of this study was to investigate the association between the PF volume and dimensions in relation to biological sex, type of neurovascular conflict (NVC), and outcome after MVD in classic TN.

METHODS: In this observational study, 84 patients with TN operated on with MVD with a preoperative head computed tomography(CT) scan were included. Eighty-two adults without TN who had undergone head CT for other reasons were included as controls. PF volume and dimensions (x-axis, y-axis, and z-axis) were evaluated on the CT scans. For the patients with TN, Barrow Neurological Institute (BNI) grade was evaluated 6 months after MVD.

RESULTS: There was no difference in PF volume or dimensions between the patients with TN and controls. Women showed a smaller volume and narrower (x-axis) PF than men, but these differences did not manifest when comparing patients with TN and controls within each sex. Patients with an NVC involving the superior cerebellar artery had a narrower (x-axis) and shorter (y-axis) PF than did patients with an NVC resulting from other arteries. PF volume or dimensions were not associated with BNI grade after MVD.

CONCLUSIONS: PF anatomy was related to the NVC type but did not differ between patients with TN and controls and was not related to the surgical outcome after MVD.

BACKGROUND: Failure to assess patients' anxiety perioperatively by means of a validated instrument makes the assessment arbitrary. Studies are lacking about how well nurse anaesthetists estimate patients' preoperative worries.

PURPOSE: To compare the nurse anaesthetists' estimations of patients' preoperative anxieties with the patients' own assessment of their anxieties.

DESIGN: Quantitative prospective design.

METHODS: Eighty-five pairs of patients and nurse anaesthetists in two ambulatory surgery units in a university hospital in Sweden were included. Patients' perioperative anxieties were graded using the Numeric Visual Analogue Anxiety Scale.

RESULTS: The nurse anaesthetist overestimated the patients' level of preoperative anxiety in 53% of patients and underestimated patients' anxieties in 31% of the patients. Consensus was seen in 16% of the pairs. In fifty-six pairs (65%), the difference between the estimation of level of patients' anxiety according to Numeric Visual Analogue Anxiety Scale was between -3 (overestimation) and +3 levels (underestimation). Median levels of anxiety were estimated as 3 within the patient group and 4 among the nurse anaesthetists.

CONCLUSIONS: Systematic assessment of patients' level of anxiety could lead to identifying patients with severe anxiety levels and to offer more individualised treatment. The patients' own estimation must form the basis for the discussion and treatment.

Repetitive monopolar short-train stimulation (STS) delivered from a suction probe enables continuous mapping and distance assessment of corticospinal tracts during asleep glioma resection. In this study, we explored this stimulation technique in awake glioma surgery. Fourteen patients with glioma involving language-related tracts were prospectively included. Continuous (3-Hz) cathodal monopolar STS (five pulses, 250 Hz) was delivered via the tip of a suction probe throughout tumor resection while testing language performance. At 70 subcortical locations, surgery was paused to deliver STS in a steady suction probe position. Monopolar STS influence on language performance at different subcortical locations was separated into three groups. Group 1 represented locations where STS did not produce language disturbance. Groups 2 and 3 represented subcortical locations where STS produced language interference at different threshold intensities (>= 7.5 and <= 5 mA, respectively). For validation, bipolar Penfield stimulation (PS; 60 Hz for 3 s) was used as a "gold standard" comparison method to detect close proximity to language-related tracts and classified as positive or negative regarding language interference. There was no language interference from STS in 28 locations (Group 1), and PS was negative for all sites. In Group 2 (STS threshold >= 7.5 mA; median, 10 mA), there was language interference at 18 locations, and PS (median, 4 mA) was positive in only one location. In Group 3 (STS threshold <= 5 mA; median, 5 mA), there was language interference at 24 locations, and positive PS (median 4 mA) was significantly (p < 0.01) more common (15 out of 24 locations) compared with Groups 1 and 2. Despite the continuous stimulation throughout tumor resection, there were no seizures in any of the patients. In five patients, temporary current spread to the facial nerve was observed. We conclude that continuous subcortical STS is feasibly also in awake glioma surgery and that no language interference from STS or interference at >= 7.5 mA seems to indicate safe distance to language tracts as judged by PS comparisons. STS language interference at STS <= 5 mA was not consistently confirmed by PS, which needs to be addressed.

Introduction: A range of adverse events (AEs) may occur in patients with subarachnoid hemorrhage (SAH). Endovascular treatment is commonly used to prevent aneurysm re-rupture.

Research question: The aim of this study was to identify AEs related to endovascular treatment, analyze risk factors for AEs and how AEs affect patient outcome.

Material and methods: Patients with aneurysmal SAH admitted to all neurosurgical centers in Sweden during a 3.5-year period (2014-2018) were prospectively registered. AEs related to endovascular aneurysm treatment were thromboembolic events, aneurysm re-rupture, vessel dissection and puncture site hematoma. Potential risk factors for the AEs were analyzed using multivariate logistic regression. Functional outcome was assessed at one year using the extended Glasgow outcome scale.

Results: In total, 1037 patients were treated for ruptured aneurysms. Of which, 715 patients were treated with endovascular occlusion. There were 115 AEs reported in 113 patients (16%). Thromboembolic events were noted in 78 patients (11%). Aneurysm re-rupture occurred in 28 (4%), vessel dissection in 4 (0.6%) and puncture site hematoma in 5 (0.7%). Blister type aneurysm, aneurysm smaller than 5 mm and endovascular techniques other than coiling were risk factors for treatment-related AEs. At follow-up, 230 (32%) of the patients had unfavorable outcome. Patients suffering intraprocedural aneurysm re-rupture were more likely to have unfavorable outcome (OR 6.9, 95% CI 2.3-20.9).

Discussion and conclusion: Adverse events related to endovascular occlusion of a ruptured aneurysm were seen in 16% of patients. Aneurysm re-rupture during endovascular treatment was associated with increased risk of unfavorable functional outcome.

Background Adverse events (AEs) or complications may arise secondary to the treatment of aneurysmal subarachnoid haemorrhage (SAH). The aim of this study was to identify AEs associated with microsurgical occlusion of ruptured aneurysms, as well as to analyse their risk factors and impact on functional outcome.

Methods Patients with aneurysmal SAH admitted to the neurosurgical centres in Sweden were prospectively registered during a 3.5-year period (2014–2018). AEs were categorised as intraoperative or postoperative. A range of variables from patient history and SAH characteristics were explored as potential risk factors for an AE. Functional outcome was assessed approximately 1 year after the bleeding using the extended Glasgow Outcome Scale.

Results In total, 1037 patients were treated for ruptured aneurysms, of which, 322 patients were treated with microsurgery. There were 105 surgical AEs in 97 patients (30%); 94 were intraoperative AEs in 79 patients (25%). Aneurysm rerupture occurred in 43 patients (13%), temporary occlusion of the parent artery >5 min in 26 patients (8%) and adjacent vessel injury in 25 patients (8%). High Fisher grade and brain oedema on CT were related to increased risk of AEs. At follow-up, 38% of patients had unfavourable outcome. Patients suffering AEs were more likely to have unfavourable outcome (OR 2.3, 95% CI 1.10 to 4.69).

Conclusion Intraoperative AEs occurred in 25% of patients treated with microsurgery for ruptured intracerebral aneurysm in this nationwide survey. Although most operated patients had favourable outcome, AEs were associated with increased risk of unfavourable outcome.

IMPORTANCE: The effect of a physical property of irrigation fluid (at body vs room temperature) on recurrence rate in the evacuation of chronic subdural hematoma (cSDH) needs further study.

OBJECTIVE: To explore whether irrigation fluid temperature has an influence on cSDH recurrence.

DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter randomized clinical trial performed between March 16, 2016, and May 30, 2020. The follow-up period was 6 months. The study was conducted at 3 neurosurgical departments in Sweden. All patients older than 18 years undergoing cSDH evacuation during the study period were screened for eligibility in the study.

INTERVENTIONS: The study participants were randomly assigned by 1:1 block randomization to the cSDH evacuation procedure with irrigation fluid at room temperature (RT group) or at body temperature (BT group).

MAIN OUTCOMES AND MEASURES: The primary end point was recurrence requiring reoperation within 6 months. Secondary end points were mortality, health-related quality of life, and complication frequency.

RESULTS: At 6 months after surgery, 541 patients (mean [SD] age, 75.8 [9.8] years; 395 men [73%]) had a complete follow-up according to protocol. There were 39 of 277 recurrences (14%) requiring reoperation in the RT group, compared with 16 of 264 recurrences (6%) in the BT group (odds ratio, 2.56; 95% CI, 1.38-4.66; P < .001). There were no significant differences in mortality, health-related quality of life, or complication frequency.

CONCLUSIONS AND RELEVANCE: In this study, irrigation at body temperature was superior to irrigation at room temperature in terms of fewer recurrences. This is a simple, safe, and readily available technique to optimize outcome in patients with cSDH. When irrigation is used in cSDH surgery, irrigation fluid at body temperature should be considered standard of care.

TRIAL REGISTRATION: ClincalTrials.gov Identifier: NCT02757235.

Diffuse brain injury is better described as multi-focal, where pathology can be found adjacent to seemingly uninjured neural tissue. In experimental diffuse brain injury, pathology and pathophysiology have been reported far more lateral than predicted by the impact site. We hypothesized that local thickening of the rodent skull at the temporal ridges serves to focus the intracranial mechanical forces experienced during brain injury and generate predictable pathology. We demonstrated local thickening of the skull at the temporal ridges using contour analysis on magnetic resonance imaging. After diffuse brain injury induced by midline fluid percussion injury (mFPI), pathological foci along the anterior-posterior length of cortex under the temporal ridges were evident acutely (1, 2, and 7 days) and chronically (28 days) post-injury by deposition of argyophilic reaction product. Area CA3 of the hippocampus and lateral nuclei of the thalamus showed pathological change, suggesting that mechanical forces to or from the temporal ridges shear subcortical regions. A proposed model of mFPI biomechanics suggests that injury force vectors reflect off the skull base and radiate toward the temporal ridge, thereby injuring ventral thalamus, dorsolateral hippocampus, and sensorimotor cortex. Surgically thinning the temporal ridge before injury reduced injury-induced inflammation in the sensorimotor cortex. These data build evidence for temporal ridges of the rodent skull to contribute to the observed pathology, whether by focusing extracranial forces to enter the cranium or intracranial forces to escape the cranium. Pre-clinical investigations can take advantage of the predicted pathology to explore injury mechanisms and treatment efficacy.

Research in the field of traumatic brain injury has until now heavily relied on the use of animal models to identify potential therapeutic approaches. However, a long series of failed clinical trials has brought many scientists to question the translational reliability of pre-clinical results obtained in animals. The search for an alternative to conventional models that better replicate human pathology in traumatic brain injury is thus of the utmost importance for the field. Recently, orthotopic xenotransplantation of human brain organoids into living animal models has been achieved. This review summarizes the existing literature on this new method, focusing on its potential applications in preclinical research, both in the context of cell replacement therapy and disease modelling. Given the obvious advantages of this approach to study human pathologies in an in vivo context, we here critically review its current limitations while considering its possible applications in traumatic brain injury research.

Neurosarcoidosis presents a diagnostic challenge in clinical settings, as it has no pathognomonic symptoms or signs and a wide range of differential diagnoses. The aim of this report is to present the pathological features of our group of patients, obtained through a systematic diagnostic approach. This retrospective cohort study enrolled all adult patients primarily diagnosed with neurosarcoidosis at the neurology department of a tertiary center in Sweden over a period of 30 years, from 1990 to 2021. We identified 90 patients, 54 with possible neurosarcoidosis and 36 with probable neurosarcoidosis. CNS biopsy revealed an alternative diagnosis for 24 patients, who were then excluded. The collected data from medical records included demographic and clinical characteristics, systemic and/or neurological isolated involvement, various laboratory tests, including cerebrospinal fluid (CSF), serum analysis, imaging studies (MRI, FDG-PET/CT, and HRCT), nerve conduction studies, electromyography, and pathology reports of central nervous system (CNS), and extra-neural tissue biopsies. Sixty-six patients were included in our cohort. The median age at onset of symptoms was 49 years, with a similar sex distribution. Cranial neuropathies (38%), motor deficit (32%), headache (16%), and pituitary dysfunction (12%) were the most common presenting features. CSF studies were abnormal in 77% of the patients, who showed lymphocytosis (57%), elevated protein (44%), oligoclonal bands (40%), elevated ACE (28%), and raised T lymphocyte CD4(+)/CD8(+) ratios (13%). Strikingly, MRI showed that 17% of the patients presented with isolated pituitary gland lesions. FDG-PET/CT was performed in 22 patients (33%) and confirmed systemic sarcoidosis in 11. Despite our extensive workup, the final classification for our patients only allowed for a definite diagnosis in 14 patients; the remainder were classified as probable (32) or possible (20) neurosarcoidosis. Since 2007, the employment of a structured laboratory and imaging approach and the increasing number of CNS biopsies have facilitated and improved the process of correct attribution in patients with presumptive neurosarcoidosis, especially in patients with isolated neurological lesions. We highlight a higher frequency of pituitary lesions due to neurosarcoidosis than has been classically described. A detailed laboratory diagnostic workup is included.