To what extent does the subarachnoid cerebrospinal fluid (CSF) compartment communicate directly with the extravascular compartment of human brain tissue? Interconnection between the subarachnoid CSF compartment and brain perivascular spaces is reported in some animal studies, but with controversy, and in vivo CSF tracer studies in humans are lacking. In the present work, we examined the distribution of a CSF tracer in the human brain by MRI over a prolonged time span. For this, we included a reference cohort, representing close to healthy individuals, and a cohort of patients with dementia and anticipated compromise of CSF circulation (idiopathic normal pressure hydrocephalus). The MRI contrast agent gadobutrol, which is confined to the extravascular brain compartment by the intact blood-brain barrier, was used as a CSF tracer. Standardized T1-weighted MRI scans were performed before and after intrathecal gadobutrol at defined time points, including at 24 hours, 48 hours, and 4 weeks. All MRI scans were aligned and brain regions were segmented using FreeSurfer, and changes in normalized T1 signals over time were quantified as percentage change from baseline. The study provides in vivo evidence of access to all human brain subregions of a substance administered intrathecally. Clearance of the tracer substance was delayed in the dementia cohort. These observations translate previous findings in animal studies into humans and open new prospects concerning intrathecal treatment regimens, extravascular contrast-enhanced MRI, and assessment of brain clearance function.
It remains an enigma why human beings spend one-third of their life asleep. Experimental data suggest that sleep is required for clearance of waste products from brain metabolism. This has, however, never been verified in humans. The primary aim of the present study was to examine in vivo whether one night of total sleep deprivation affects molecular clearance from the human brain. Secondarily, we examined whether clearance was affected by subsequent sleep. Multiphase MRI with standardized T1 sequences was performed up to 48 h after intrathecal administration of the contrast agent gadobutrol (0.5 ml of 1 mmol/ml), which served as a tracer molecule. Using FreeSurfer software, we quantified tracer enrichment within 85 brain regions as percentage change from baseline of normalized T1 signals. The cerebral tracer enrichment was compared between two cohorts of individuals; one cohort (n = 7) underwent total sleep deprivation from Day 1 to Day 2 (sleep deprivation group) while an age and gender-matched control group (n = 17; sleep group) was allowed free sleep from Day 1 to Day 2. From Day 2 to 3 all individuals were allowed free sleep. The tracer enriched the brains of the two groups similarly. Sleep deprivation was the sole intervention. One night of sleep deprivation impaired clearance of the tracer substance from most brain regions, including the cerebral cortex, white matter and limbic structures, as demonstrated on the morning of Day 2 after intervention (sleep deprivation/sleep). Moreover, the impaired cerebral clearance in the sleep deprivation group was not compensated by subsequent sleep from Day 2 to 3. The present results provide in vivo evidence that one night of total sleep deprivation impairs molecular clearance from the human brain, and that humans do not catch up on lost sleep.
BackgroundChronic subdural haematoma (CSDH) is a common entity in neurosurgery with a considerable postoperative recurrence rate. Computerised tomography (CT) scanning remains the most important diagnostic test for this disorder. The aim of this study was to characterise the relationship between the recurrence of CSDH after treatment with burr-hole irrigation and closed-system drainage technique and CT scan features of these lesions to assess whether CT findings can be used to predict recurrence.MethodsWe investigated preoperative and postoperative CT scan features and recurrence rate of 107 consecutive adult surgical cases of CSDH and assessed any relationship with univariate and multivariate regression analyses.ResultsSeventeen patients (15.9 %) experienced recurrence of CSDH. The preoperative haematoma volume, the isodense, hyperdense, laminar and separated CT densities and the residual total haematoma cavity volume on the 1st postoperative day after removal of the drainage were identified as radiological predictors of recurrence. If the preoperative haematoma volume was under 115 ml and the residual total haematoma cavity volume postoperatively was under 80 ml, the probability of no recurrence was very high (94.4 % and 97.4 % respectively).ConclusionsThese findings from CT imaging may help to identify patients at risk for postoperative recurrence.
The intervention appeared to speed up recovery for patients with dizziness and balance problems after traumatic brain injury. However, the benefits had dissipated two months after the end of the intervention.
Aims To compare operative and nonoperative treatment for displaced distal radius fractures in patients aged over 65 years. Methods A total of 100 patients were randomized in this non-inferiority trial, comparing cast immobilization with operation with a volar locking plate. Patients with displaced AO/OTA A and C fractures were eligible if one of the following were found after initial closed reduction: 1) dorsal angulation > 10°; 2) ulnar variance > 3 mm; or 3) intra-articular step-off > 2 mm. Primary outcome measure was the abbreviated version of the Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) after 12 months. Secondary outcome measures were the Patient-Rated Wrist and Hand Evaluation (PRWHE), EuroQol-5 dimensions 5-level questionnaire (EQ-5D-5L), range of motion (ROM), grip strength, “satisfaction with wrist function” (score 0 to 10), and complications. Results In all, 89 women and 11 men were included. Mean age was 74 years (65 to 91). Nonoperative treatment was non-inferior to operation with a five-point difference in median QuickDASH after 12 months (p = 0.206). After three and six months QuickDASH favoured the operative group (p = 0.010 and 0.030). Median values for PRWHE were 19 (interquartile range (IRQ) 10 to 32) in the operative group versus ten (IQR 1 to 31) in the nonoperative group at three months (p = 0.064), nine (IQR 2 to 20) versus five (IQR 0 to 13) (p = 0.020) at six months, and two (IQR 0 to 12) versus zero (IQR 0 to 8) (p = 0.019) after 12 months. Range of motion was similar between the groups. The EQ-5D-5L index score was better (mean difference 0.07) in the operative group at three and 12 months (p = 0.008 and 0.020). The complication rate was similar (p = 0.220). The operated patients were more satisfied with wrist function (median 8 (IQR 6 to 9) vs 6 (IQR 5 to 7) at three months, p = 0.002; 9 (IQR 7 to 9) vs 8 (IQR 6 to 8) at six months, p = 0.002; and 10 (IQR 8 to 10) vs 8 (IQR 7 to 9) at 12 months, p < 0.001). Conclusion Nonoperative treatment was non-inferior to operative treatment based on QuickDASH after one year. Patients in the operative group had a faster recovery and were more satisfied with wrist function. Results from previous trials comparing operative and nonoperative treatment for displaced distal radius fractures in the elderly vary between favouring the operative group and showing similar results between the treatments. This randomized trial suggests that most elderly patients may be treated nonoperatively. Cite this article: Bone Joint J 2021;103-B(2):247–255.
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