The added value of risk assessment and subsequent targeted treatment for epileptic seizures after stroke: An early-HTA analysis.

INTRODUCTION: The development of post-stroke epilepsy (PSE) is related to a worse clinical outcome in stroke patients. Adding a biomarker to the clinical diagnostic process for the prediction of PSE may help to establish targeted and personalized treatment for high-risk patients, which could lead to improved patient outcomes. We assessed the added value of a risk assessment and subsequent targeted treatment by conducting an early Health Technology Assessment. METHODS: Interviews were conducted with four relevant stakeholders in the field of PSE to obtain a realistic view of the current healthcare and their opinions on the potential value of a PSE risk assessment and subsequent targeted treatment. The consequences on quality of life and costs of current care of a hypothetical care pathway with perfect risk assessment were modeled based on information from a literature review and the input from the stakeholders. Subsequently, the maximum added value (the headroom) was calculated. Sensitivity analyses were performed to test the robustness of this result to variation in assumed input parameters, i.e. the accuracy of the risk assessment, the efficacy of anti-seizure medication (ASM), and the probability of patients expected to develop PSE. RESULTS: All stakeholders considered the addition of a predictive biomarker for the risk assessment of PSE to be of value. The headroom amounted to €12,983. The sensitivity analyses demonstrated that the headroom remained beneficial when varying the accuracy of the risk assessment, the ASM efficacy, and the number of patients expected to develop PSE. DISCUSSION: We showed that a risk assessment for PSE development is potentially valuable. This work demonstrates that it is worthwhile to undertake clinical studies to evaluate biomarkers for the prediction of patients at high risk for PSE and to assess the value of targeted prophylactic treatment.

Imaging Interstitial Fluid With MRI: A Narrative Review on the Associations of Altered Interstitial Fluid With Vascular and Neurodegenerative Abnormalities.

Interstitial fluid (ISF) refers to the fluid between the parenchymal cells and along the perivascular spaces (PVS). ISF plays a crucial role in delivering nutrients and clearing waste products from the brain. This narrative review focuses on the use of MRI techniques to measure various ISF characteristics in humans. The complementary value of contrast-enhanced and noncontrast-enhanced techniques is highlighted. While contrast-enhanced MRI methods allow measurement of ISF transport and flow, they lack quantitative assessment of ISF properties. Noninvasive MRI techniques, including multi-b-value diffusion imaging, free-water-imaging, T2 -decay imaging, and DTI along the PVS, offer promising alternatives to derive ISF measures, such as ISF volume and diffusivity. The emerging role of these MRI techniques in investigating ISF alterations in neurodegenerative diseases (eg, Alzheimer's disease and Parkinson's disease) and cerebrovascular diseases (eg, cerebral small vessel disease and stroke) is discussed. This review also emphasizes current challenges of ISF imaging, such as the microscopic scale at which ISF has to be measured, and discusses potential focus points for future research to overcome these challenges, for example, the use of high-resolution imaging techniques. Noninvasive MRI methods for measuring ISF characteristics hold significant potential and may have a high clinical impact in understanding the pathophysiology of neurodegenerative and cerebrovascular disorders, as well as in evaluating the efficacy of ISF-targeted therapies in clinical trials. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Cerebral Microvascular Perfusion Assessed in Elderly Adults by Spin-Echo Dynamic Susceptibility Contrast MRI at 7 Tesla.

Perfusion measures of the total vasculature are commonly derived with gradient-echo (GE) dynamic susceptibility contrast (DSC) MR images, which are acquired during the early passes of a contrast agent. Alternatively, spin-echo (SE) DSC can be used to achieve specific sensitivity to the capillary signal. For an improved contrast-to-noise ratio, ultra-high-field MRI makes this technique more appealing to study cerebral microvascular physiology. Therefore, this study assessed the applicability of SE-DSC MRI at 7 T. Forty-one elderly adults underwent 7 T MRI using a multi-slice SE-EPI DSC sequence. The cerebral blood volume (CBV) and cerebral blood flow (CBF) were determined in the cortical grey matter (CGM) and white matter (WM) and compared to values from the literature. The relation of CBV and CBF with age and sex was investigated. Higher CBV and CBF values were found in CGM compared to WM, whereby the CGM-to-WM ratios depended on the amount of largest vessels excluded from the analysis. CBF was negatively associated with age in the CGM, while no significant association was found with CBV. Both CBV and CBF were higher in women compared to men in both CGM and WM. The current study verifies the possibility of quantifying cerebral microvascular perfusion with SE-DSC MRI at 7 T.

Assessment of the clinical feasibility of detecting subtle blood-brain barrier leakage in cerebral small vessel disease using dynamic susceptibility contrast MRI.

PURPOSE: Cerebral small vessel disease (cSVD) involves several pathologies affecting the small vessels, including blood-brain barrier (BBB) impairment. Dynamic susceptibility contrast (DSC) MRI is sensitive to both blood perfusion and BBB leakage, and correction methods may be crucial for obtaining reliable perfusion measures. These methods might also be applicable to detect BBB leakage itself. This study investigated to what extent DSC-MRI can measure subtle BBB leakage in a clinical feasibility setting. METHODS: In vivo DCE and DSC data were collected from fifteen cSVD patients (71 (±10) years, 6F/9M) and twelve elderly controls (71 (±10) years, 4F/8M). DSC-derived leakage fractions were obtained using the Boxerman-Schmainda-Weisskoff method (K2). K2 was compared with the DCE-derived leakage rate Ki, obtained from Patlak analysis. Subsequently, differences were assessed between white matter hyperintensities (WMH), cortical gray matter (CGM), and normal-appearing white matter (NAWM). Additionally, computer simulations were performed to assess the sensitivity of DSC-MRI to BBB leakage. RESULTS: K2 showed significant differences between tissue regions (P < 0.001 for CGM-NAWM and CGM-WMH, and P = 0.001 for NAWM-WMH). Conversely, according to the computer simulations the DSC sensitivity was insufficient to measure subtle BBB leakage, as the K2 values were below the derived limit of quantification (4∙10-3 min-1). As expected, Ki was elevated in the WMH compared to CGM and NAWM (P < 0.001). CONCLUSIONS: Although clinical DSC-MRI seems capable to detect subtle BBB leakage differences between WMH and normal-appearing brain tissue it is not recommended. K2 as a direct measure for subtle BBB leakage remains ambiguous as its signal effects are due to mixed T1- and T2∗-weighting. Further research is warranted to better disentangle perfusion from leakage effects.

A Comprehensive View on MRI Techniques for Imaging Blood-Brain Barrier Integrity.

The blood-brain barrier (BBB) is the interface between the blood and brain tissue, which regulates the maintenance of homeostasis within the brain. Impaired BBB integrity is increasingly associated with various neurological diseases. To gain a better understanding of the underlying processes involved in BBB breakdown, magnetic resonance imaging (MRI) techniques are highly suitable for noninvasive BBB assessment. Commonly used MRI techniques to assess BBB integrity are dynamic contrast-enhanced and dynamic susceptibility contrast MRI, both relying on leakage of gadolinium-based contrast agents. A number of conceptually different methods exist that target other aspects of the BBB. These alternative techniques make use of endogenous markers, such as water and glucose, as contrast media. A comprehensive overview of currently available MRI techniques to assess the BBB condition is provided from a scientific point of view, including potential applications in disease. Improvements that are required to make these techniques clinically more easily applicable will also be discussed.