Anders Eklund

Selective antegrade cerebral perfusion (SACP) maintains cerebral perfusion during aortic arch surgery and is mainly achieved by cannulating unilaterally (uSACP) or bilaterally (bSACP). The choice of applying uSACP or bSACP is often made according to institutional practice, whereas neurological complications may be reduced if the approaches instead were applied according to the patient’s individual cerebral collateral circulation. However, no method for predicting intraoperative cerebral collateral capacity is currently available. This study evaluates a computational method for predicting the cerebral perfusion pressure (CPP) in patients undergoing aortic arch surgery with SACP. Twenty-two patients underwent elective aortic arch surgery with bSACP, including a five-minute intervention of right-sided uSACP. Patients preoperatively underwent computed tomography angiography and 4D flow magnetic resonance imaging to assess patient-specific arterial anatomy and blood flows. Computational fluid dynamics modelling estimated the vascular resistance of the vascular beds distal of the segmented arterial anatomy. Based on these resistances, a subsequent model predicted CPP during uSACP and bSACP given intraoperatively measured input. There was no difference between predicted and measured left side CPP for uSACP (-3.0 ± 11.2 mmHg, p=0.25; r=0.75, p<0.001) or bSACP (-0.4 ± 5.7 mmHg, p=0.78; r=0.94, p<0.001). There was good group level agreement (90% CI, uSACP: [-7.5, 1.4]; bSACP: [-2.6, 1.9]) whereas limits of agreement showed substantial spread (uSACP: [-24.9, 18.9], bSACP: [-11.5, 10.8]). The new method predicted CPP on group level, while improved individual prediction accuracy may be achievable through refined arterial segmentation and more accurate estimation of intraoperative vascular resistances.

Background: Although clinical evaluation, radiological findings, and supplementary tests are routinely used to diagnose idiopathic normal pressure hydrocephalus (INPH), the large variability in surgical outcomes raises the question of whether diagnostic radiological markers truly reflect the typical clinical gait impairment. Gait disorder (GD) and ventriculomegaly (VM) are both common in older adults and may coincide by chance, potentially contributing to this inconsistency in results. This study aimed to determine the prevalence of typical INPH-related higher-level gait disorder (HLGD), diagnosed independently of imaging, and assess its association with VM and other MRI features. Methods: In this case-control study, 6467 individuals age 65–84 years were screened for GD per questionnaire. Physicians with experience of neurological GD identified cases with HLGD and matched controls without GD through clinical evaluation of 1047 of these individuals. Subsequently, brain MRI ( n = 909) or CT ( n = 98) was performed. After exclusions, 81 with HLGD and 192 controls remained. Radiological hydrocephalus features were compared between the groups. Results: The prevalence of HLGD in the general older population was 5.8%. For HLGD combined with Evans Index (EI)>0.3, it was 3.7%, and 1.7% had HLGD with Disproportionately Enlarged Subarachnoid space Hydrocephalus (DESH). The estimated prevalence of asymptomatic VM, i.e. EI > 0.3 without GD, was 24%, and 4.1% had asymptomatic VM with DESH. Individuals with HLGD were older and performed worse on cognitive tests. Radiology revealed higher ventricular volumes and EI, and a more acute callosal angle in HLGD versus controls. DESH was also more frequent in HLGD (29% vs 7%, p < 0.001). Despite group-level differences, individual overlap was substantial. MRI markers showed poor to moderate ability to discriminate HLGD (AUC 0.614–0.765) from normal gait. Conclusions: In this population-based case-control study, both HLGD and EI > 0.3 were common. EI > 0.3 occurred more frequently with HLGD, but it was also common in asymptomatic individuals, indicating that ventriculomegaly is not specific to HLGD. Most MRI biomarkers showed limited ability to distinguish HLGD from normal gait, although lateral ventricular volume divided by total intracranial volume (relative ventricular volume) was the most informative. The frequent occurrence of EI > 0.3 and DESH in asymptomatic individuals highlights the need for longitudinal studies to clarify prognosis in these individuals.

Objective: Idiopathic normal pressure hydrocephalus (INPH) is a treatable neurological condition, yet predicting which patients will benefit from a cerebrospinal fluid shunt remains challenging. Structural brain MRI is a core part of the diagnostic workup, but traditional radiological measures show limited predictive accuracy. This study aimed to assess whether deep learning and radiomics-based machine learning approaches can provide clinically useful predictions of shunt outcome based on preoperative MRI. Methods: We investigated 149 shunted INPH patients with available preoperative T1-weighted, T2-weighted, and FLAIR images. Patients were classified as responders (n = 113) or non-responders (n = 36) based on postoperative gait speed improvement. For INPH, this is a large sample with typical outcome distribution. Three artificial intelligence approaches were tested: a late-fusion ensemble of multiple 3D convolutional neural networks; a multimodal intermediate fusion model; and radiomics-based machine learning models trained on features extracted from whole-brain masks. Models were assessed using 10-fold cross-validation. The best performing model on the validation set was selected from each approach. Performance metrics included the area under the receiving operating characteristic curve (AUROC), sensitivity, and specificity. Results: Performance was considered poor in all models, and none reached an area under the receiving operating characteristic curve above 70%. Of the three methodologies, the best performance was achieved with a radiomics-based model (Linear Discriminant Analysis classifier on T1-weighted images) which achieved an AUROC of 63.7%. In a reduced subset of clearly separated responders and non-responders (n = 72), the best model (late fusion ensemble of 5 convolutional neural networks) reached an AUROC of 69.2%. Conclusions: Despite the use of advanced artificial intelligence techniques, structural MRI alone were insufficient for reliably predicting gait outcome after surgery in idiopathic normal pressure hydrocephalus. To capture the complexity of the condition and enable clinically meaningful predictions, our findings indicate the need for research investigating multimodal input and using large multi-center datasets.

Spaceflight-associated neuro-ocular syndrome (SANS) poses a significant risk for astronauts, being linked to intracranial pressure (ICP) changes in microgravity. Investigating ICP in space has been challenging. We evaluated a telemetric lumbar ICP monitoring system that shows promise for investigating microgravity-induced intracranial pressure changes in astronauts. Despite limitations in pulse amplitude analysis and pressure underestimation, the system’s long-term stability and overall performance support its recommendation for SANS research in space.

According to glymphatic system theory, cerebrospinal fluid (CSF) perfuses the brain’s interstitial space to support waste clearance, but the magnitude of this flow and the outflow pathway of interstitial fluid (ISF) in humans remain uncertain. To achieve flow quantification, we applied a compartment-model approach applied in conjunction with serial quantitative MRI data acquired after intrathecal gadolinium administration. Using the method, we estimated CSF-to-ISF inflow to 45 ± 20 mL/h, in patients with suspected idiopathic normal pressure hydrocephalus. Tissue-specific contributions were 34 ± 14 mL/h in cortical gray matter, 11±6 mL/h in white matter, and 0.4 ± 0.3 mL/h in subcortical gray matter, suggesting that CSF perfusion occurs primarily in superficial regions near the subarachnoid space. A lack of correlation between inflow and total craniospinal system outflow (r = 0.03, P = 0.91) suggested that ISF recirculates back into CSF rather than exiting the craniospinal system via a separate route. Independent experiments in healthy older individuals using intravenous gadolinium administration supported ISF-to-CSF recirculation, where contrast material that presumably crossed the blood–brain barrier subsequently appeared in the subarachnoid space, allowing ISF-to-CSF flow quantification. These findings provide a quantitative framework for studying brain clearance in humans and support subarachnoid space recirculation as an important efflux route.

BACKGROUND AND OBJECTIVES: Glymphatic function affects brain health and could be part of the pathophysiology in idiopathic normal-pressure hydrocephalus. Elevated intracranial pressure pulsatility and increased resistance to cerebrospinal fluid (CSF) outflow (R _out ) are commonly observed in idiopathic normal-pressure hydrocephalus. Whether such alterations indicate impaired glymphatic function or affect ventricle volumetrics in ordinary elderly is unknown. We investigated the associations between CSF dynamics and changes in cognitive performance, gait, and brain MRI parameters over a 10-year period in a cohort of healthy older adults. METHODS: Twenty-nine subjects (mean age 79 ± 6, range 71-92 years) were investigated with brain MRI, clinical testing, and a CSF infusion test. MRI and clinical testing were repeated after 10 years. An automated software program was used to calculate ventricle volumes, and linear ventricle radiological indices were calculated (Evan's index, callosal angle, and z-Evan's index). CSF dynamic parameters were correlated with longitudinal changes in clinical and MRI parameters. RESULTS: In a multivariable regression model including age, sex, baseline cognitive performance, and CSF dynamic parameters, lower CSF outflow resistance was associated with better cognitive performance after 10 years (standardized β = 0.37, P = .047, n = 29). In a bivariate analysis, outflow resistance had a negative correlation to the difference in cognitive testing score between baseline and follow-up (r = −.44, 95% CI −0.701 to −0.08, P = .017, n = 29, Spearman's rho). CSF dynamic parameters were not associated with changes in gait performance or ventricle volume. Intracranial pressure pulsatility was associated with reduced callosal angle (standardized β = −0.35, P = .02, n = 29) and intracranial pressure with increased z-Evan's index (standardized β = 0.18, P = .003, n = 29). CONCLUSION: Our results provide insight into the complexity of CSF physiology and its possible role in longitudinal change in brain function and structure. Measurement of CSF outflow characteristics hold potential in furthering the understanding of glymphatic performance with regard to change in cognitive function and warrants further investigation.

After more than 50 years, there still remains a challenge and an interest to know more as well as extend and deepen our understanding of the small rapid wavelets, the oscillatory potentials (OPs), of the electroretinogram (ERG) and the neuronal adaptation of the retina. This paper summarizes the current knowledge of the rapid oscillatory response and its role in the process of neuronal adaptation in the retina. An effort has been made to enhance our ability and possibility, especially in the clinic, to interpret and use this response. The first section in short presents historic aspects, definitions and understanding of neuronal adaptation and the OPs. The second part deals with different and modern techniques and possibilities to record and measure the OPs, ffERG (full‐field ERG), mfERG (multifocal ERG), fmERG (focal macular ERG) and optimal adaptational recording conditions. The third section overviews the current apprehension of the origin(s) of the OPs. The fourth part describes the normal development of the OPs from prematurity to old age. The last section enlightens the importance of the OPs as indicators of disturbed retinal, neuronal adaptive function in different diseases in the retina.

Idiopathic normal-pressure hydrocephalus is a neurologic disorder characterized by impaired gait, balance, cognition, and bladder control in older adults. The disorder is treated with shunt surgery, but the effectiveness of shunting is unclear. We conducted a double-blind, randomized, placebo-controlled trial involving participants selected for shunt surgery on the basis of gait-velocity improvement with cerebrospinal fluid (CSF) drainage. Participants were randomly assigned to an open-shunt valve setting (opening pressure, 110 mm of water) or a placebo valve setting (opening pressure, >400 mm of water) of a noninvasively adjustable shunt. The primary outcome was the change in gait velocity 3 months after surgery. Secondary outcomes were the change at 3 months in the Tinetti scale total score (range, 0 to 28; lower scores indicate worse gait and balance), Montreal Cognitive Assessment (MoCA) score (range, 0 to 30; lower scores indicate worse cognition), and Overactive Bladder Questionnaire score (range, 0 to 100; higher scores indicate worse urinary incontinence). A total of 99 participants underwent randomization and received the assigned intervention. At 3 months, gait velocity had increased in the open-shunt group (mean [±SD] change, 0.23±0.23 m per second; assessed in 49 participants) and was unchanged in the placebo group (mean change, 0.03±0.23 m per second; assessed in 49 participants), resulting in a treatment difference of 0.21 m per second (95% confidence interval, 0.12 to 0.31; P<0.001). A significantly greater improvement in the open-shunt group than the placebo group was seen for the Tinetti scale score (mean change, 2.9 points vs. 0.5 points; P = 0.003) but not the MoCA score (1.3 points vs. 0.3 points) or the Overactive Bladder Questionnaire score (-3.3 points vs. -1.5 points). The results regarding adverse events were mixed, with more participants in the placebo group reporting falls (46% vs. 24%), an equal percentage having cerebral bleeding (2% in both groups), and more participants in the open-shunt group having subdural bleeding (12% vs. 2%) and positional headaches (59% vs. 28%). Among participants with idiopathic normal-pressure hydrocephalus who had a response to temporary CSF drainage, shunting resulted in significant improvements at 3 months in gait velocity and a measure of gait and balance but not in measures of cognition or incontinence. (Funded by the National Institute of Neurological Disorders and Stroke and the Trial Innovation Network; PENS ClinicalTrials.gov number, NCT05081128.).

Background Aquaporin-4 (AQP4) is crucial for brain fluid regulation and glymphatic system function. Idiopathic normal pressure hydrocephalus (INPH), characterized by impaired CSF flow, is often treated with shunt surgery. This study investigated AQP4 levels in INPH patients to explore its role in pathophysiology and potential as a biomarker for shunt response. Methods CSF samples from 233 INPH patients and 29 controls were analysed. AQP4 levels were compared between preoperative patients and controls, before and after shunt surgery (110 patients), and between shunt responders and non-responders (204 patients). A bead-based assay was used to measure AQP4, and outcomes were assessed by postoperative changes in maximum gait velocity. Results Preoperative AQP4 levels were lower in INPH patients (1177 ± 259 AU) than in controls (1351 ± 279 AU, p = 0.003), but the difference did not persist after adjustment for confounders (p = 0.87). Postoperatively, AQP4 levels increased (1714 ± 473 vs 1186 ± 269 AU, p < 0.001), with a modest correlation between AQP4 increase and gait improvement (rₛ = 0.22, p = 0.022). Compared with non-responders, shunt responders (130 patients) had lower preoperative AQP4 levels (1144 ± 250 vs. 1238 ± 273 AU, p = 0.016) Conclusions INPH patients presented AQP4 levels comparable to those of controls. The postoperative increase in AQP4 may result from altered CSF dynamics induced by the shunt; however, the underlying mechanism remains unclear, underscoring the need for further studies to clarify this relationship. Notably, lower preoperative AQP4 levels in shunt responders suggest a potential predictive role.

Background: Induced hypertension is used clinically to increase cerebral blood flow (CBF) in conditions such as vasospasm after subarachnoid hemorrhage. However, increased blood pressure also raises pulsatile force. Cerebrovascular compliance plays a key role in buffering flow dynamics and protecting the microcirculation, but whether it adapts to elevated pressure remains unclear. This study assessed the response of compliant cerebral arteries to induced hypertension in healthy adults using phase-contrast magnetic resonance imaging (PCMRI) and two compliance models: a two-element Windkessel (C_WK) and a simplified model (C_VP), representing the extremes of pulsatility transmission at the capillary level. Methods: Eighteen healthy adults (median age: 34 years; 9 females) underwent PCMRI at baseline and after increasing mean arterial pressure by 20% using norepinephrine (NE) infusion. PCMRI quantified CBF and cardiac output, while cerebrovascular resistance and systemic vascular resistance were derived. Flow waveforms were combined with blood pressure to assess C_WK and C_VP in CBF, ascending/descending aorta, and external carotid arteries, while corresponding regions of interest were used to calculate cross-sectional flow areas. Data are reported as median (interquartile range). Results: NE increased cerebrovascular compliance significantly; C_WK by 110% (56% to 163%; P=0.001) and C_VP by 11% (−2% to 26%; P=0.018). C_WK increased in the external carotid artery by 12% (1% to 32%; P=0.037) but did not change in the ascending or descending aorta. C_VP decreased in the descending aorta by 5% (-11% to 2%; P=0.028), with no changes in the ascending aorta or external carotid artery. Cross-sectional area of cerebral arteries contributing to CBF decreased by 5% (-17% to -3%; P=0.033), while the ascending and descending aorta areas increased by 7% (4% to 11%; P=0.012) and 8% (6% to 11%; P<0.001), respectively. Conclusion: Cerebral arteries enhanced their compliance during NE-induced hypertension, unlike systemic arteries, regardless of the assumed degree of pulsatility transmission.