RPS 311 - Illuminating the brain: neuroimaging insights into epilepsy and neuroinflammation

Author Block: R. Stepponat, M. Berger, L. Schäfer, M. S. Yildirim, J. Leinkauf, F. Fischmeister, S. Bonelli, G. Kasprian; Vienna/AT
Purpose: Pre-surgical language evaluation has remained largely unchanged for years, underscoring the need for improved methods. Given that epilepsy and language both operate as network functions, analyzing the individual functional connectome may offer greater clinical precision, enabling more accurate predictions and better-informed surgical decisions for enhanced patient care.
Methods or Background: Language is predominantly left-lateralized, and fMRI is commonly used for preoperative evaluation of lateralization by calculating the lateralization index (LI). However, a survey by Benjamin et al. highlights significant uncertainties in fMRI results among clinicians.
In this study, 46 patients with temporal lobe epilepsy and 25 healthy controls underwent preoperative fMRI. Data preprocessing was performed with fMRIPrep, and correlation maps were created using the CONN toolbox. Seed-based connectivity (SBC) analysis of core language areas, based on Fredarenko et al. 2024, was conducted, and a LI based on graph measurements (degree) was calculated. This was compared to traditional LI analysis and neuropsychological data, with all analyses conducted in native space.
Results or Findings: Results indicated that the connectivity-based lateralization index (LI) provided a more consistent measure of language lateralization compared to standard LI methods, aligning better with neuropsychological assessments. Patients with lesional epilepsy showed greater variability in lateralization compared to MR-negative patients, while healthy controls exhibited stronger left-lateralization as expected. The use of seed-based connectivity (SBC) analysis enhanced the detection of individual differences in language network organization, underscoring its potential clinical value in preoperative assessment.
Conclusion: The initial findings suggest that connectivity-based LI may improve the accuracy of preoperative language assessments. This approach offers a promising enhancement over traditional LI methods, providing more reliable insights for surgical planning and potentially leading to better predictions of post-surgical cognitive outcomes.
Limitations: -No neuropsychological data for the controls.
-Retrospective data.
Funding for this study: This study has been conducted as part of a PhD-thesis at the medical university of Vienna. Nothing to disclose.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: EK-Number: 1141/2023

Author Block: M. Ferro¹, J. Ramos², F. M. Doniselli³, G. Didato³; ¹Lisbon/PT, ²Gaia/PT, ³Milan/IT
Purpose: This study focuses on the radiological characteristics of patients with temporal lobe epilepsy and isolated amygdala enlargement (TLE-AE).We aim to assess the imaging findings, particularly in relation to amygdala size and signal alterations, and their correlation with clinical and pathological data to guide better diagnostic and therapeutic decisions.
Methods or Background: We conducted a retrospective analysis of 143 brain MRI scans from adult patients at a tertiary neurology center. Forty-one patients with TLE-AE were selected. Imaging was reviewed by two neuroradiologists for amygdala size and T2-hyperintensity. Fluorodeoxyglucose-PET (FDG-PET) data were also included for a subgroup of patients.Amygdala signal alterations were quantified and correlated with clinical, neurophysiological, and pathological findings. Statistical analyses assessed relationships between imaging features and clinical outcomes.
Results or Findings: Out of 41 patients, 32% had bilateral amygdala enlargement, while the remainder had unilateral findings. T2-hyperintensity was noted in 65.9% of cases, significantly correlating with amygdala enlargement. FDG-PET showed temporomesial hypometabolism in 64% of patients, further supporting the epileptogenic involvement of the amygdala.Surgical pathology confirmed various underlying etiologies, including gliosis, low-grade tumors, and inflammatory infiltrates. Post-surgical outcomes were favorable, with 70.6% of operated patients being seizure-free at last follow-up.
Conclusion: Radiologically, amygdala enlargement with or without T2-hyperintensity is a significant marker of TLE, often associated with underlying structural abnormalities or inflammation. FDG-PET is a valuable adjunct for identifying hypometabolic regions corresponding to AE, supporting its role in the epileptic network.MRI findings, combined with surgical evaluation, can improve clinical outcomes in TLE-AE patients, particularly those with drug-resistant epilepsy.
Limitations: The study's retrospective nature and variability in MRI protocols over time limit the consistency of radiological findings. Additionally, not all patients underwent advanced imaging techniques, such as PET or follow-up MRIs, reducing the ability to track longitudinal changes.
Funding for this study: None.
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information: Retrospective study.

Author Block: S. Chambers, H. Shayeste, P. Lazen, L. Haider, E. Pataraia, G. Kasprian, W. Bogner, S. Trattnig, G. Hangel; Vienna/AT
Purpose: Identifying epileptogenic foci is essential in therapy-planning and predictive for post-operative seizure freedom in epilepsy. In this work we present a novel MRSI technique (CRT-FID) at 7T, allowing for ultra-high resolution whole-brain maps in focal epilepsy. We offer a qualitative analysis of its feasibility in identifying and characterizing metabolic alterations over multiple pathologies.
Methods or Background: Following informed written consent, forty-two patients with focal epilepsy (16-52 years, 21 females/21 males) underwent a 3D-MRSI protocol in 15min with a 3.4 mm isotropic resolution at 7T using a 32Rx/1Tx-coil. Data processing involved spectral quantification and ratio mapping of Glu, Gln, Ins, tCho, tCr and NAA normalized to NAA and tCr. Furthermore, the concentration estimates of Glu and Gln were qualitatively assessed in seizure onset zones.
Results or Findings: Though we could find no consistent metabolic pattern throughout pathologies, ratio maps showed high detectability of lesions, identifying alterations in seizure onset zones in 78,6% when normalized to NAA. This detection rate was reduced to 71,2% when normalized to creatine. Of the assessed ratios, Ins/tNAA and Cho/tNAA showed highest stability across patients, whereas Glu/tNAA and Gln/tNAA showed varying directionality of changes.
Assessing these changes further in relation to clinical parameters such as the seizure frequency, we found a trend for relative increases of Gln/Glu in patients with low seizure frequencies and the inverse for high seizure frequencies.
Conclusion: 7T CRT-FID-MRSI shows promising results in identifying metabolic alterations in patients suffering from focal epilepsy, even in the absence of structural lesions.
Furthermore, this orientational study may point to an altered glutamate/glutamine cycle in epilepsy, potentially the result of altered energy metabolism pathways in chronic epilepsy.
Limitations: This study is limited by the small cohort size and qualitative nature of the analysis.
Funding for this study: This research was funded by the FWF grant 10.55776/KLI1121, of the Mayor of the Federal Capital Vienna (Project Number 21186).
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: Ethic committee number: EK 1039/2020

Author Block: S. Capelli¹, A. Caroli¹, G. Pezzetti², F. Ferretti³, R. Vercesi⁴, P. Cinque⁴, S. Gerevini²; ¹Ranica/IT, ²Bergamo/IT, ³London/UK, ⁴Milan/IT
Purpose: Symptomatic cerebrospinal fluid (CSF) HIV escape is an infrequent but severe condition occurring in persons living with HIV (PLWH) undergoing combination antiretroviral therapy (cART). It is characterized by HIV-RNA in the CSF despite being undetectable in plasma. Similarly to HIV encephalitis in cART-untreated PLWH (HIV-ENC), HIV CSF escape (HIV-ESC) is accompanied by neurological impairments and brain MRI alterations. This study aimed to investigate the neuroimaging features of HIV-ESC in comparison to HIV-ENC and neuro-asymptomatic controls.
Methods or Background: Brain structural and microstructural alterations were quantified in: HIV-ESC (n=12), HIV-ENC (n=10), neuro-asymptomatic PLWH (n=11) and neuro-asymptomatic HIV-negative controls (n=12). The quantitative analysis included measurements of normalized FLAIR signal intensity, Apparent Diffusion Coefficient (ADC) from diffusion-weighted MRI, and brain tissue volumes from T1-weighted MRI.
Results or Findings: Both HIV-ESC and HIV-ENC demonstrated significantly higher FLAIR signal intensity in white matter (WM), elevated ADC values in both white and gray matter (GM) and reduced GM volumes as compared to neuro-asymptomatic controls, while the HIV-ESC group had higher WM volumes compared to HIV-ENC. In the HIV-ESC group, GM ADC values were negatively correlated with nadir CD4+ T-cell counts, while GM volume showed a positive correlation. In contrast, in HIV-ENC, WM ADC, FLAIR signal intensity, and WM volume all positively correlated with nadir and current CD4+ T-cell counts.
Conclusion: WM hyperintensities and increased ADC values in HIV-ESC and HIV-ENC reflect active WM damage, while reduced GM volumes are indicative of long-term brain atrophy. However, the higher WM volume in HIV-ESC suggests persistent inflammation. These findings, along with their correlation to laboratory data, support the hypothesis that inflammation is the primary mechanism of brain damage in HIV-ESC.
Limitations: Retrospective study with limited patient sample and lack of a standardized MRI protocol across all subjects.
Funding for this study: National Institutes of Health (NIH); University of California, San Francisco (UCSF)
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The study was approved by “Comitato Etico IRCCS Ospedale San Raffaele” on 15/12/2016 (ref. 235/2015)

Author Block: T. Fakhreddine¹, A. Tamanti¹, C. Salvatore², D. Calderaro¹, S. Ziccardi¹, M. Calabrese¹, A. Fattorini¹, I. Castiglioni², F. B. B. Pizzini¹; ¹Verona/IT, ²Milan/IT
Purpose: Progression independent of relapse activity (PIRA) is the primary factor contributing to irreversible disability accumulation in relapsing multiple sclerosis (MS). This study aimed to investigate differences in brain volumes through Magnetic Resonance Imaging (MRI).
Methods or Background: We conducted a retrospective study with MS patients with and without cognitive PIRA who performed T1-weighted 3D MRI study (at baseline and at 24-months follow-up) at the Verona University Hospital. The TRACE4AD™ medical-device software (DeepTrace Technologies, Italy) performed automatic structural brain segmentation from MR scans into 53 regions and calculated corresponding total volumes and asymmetry indices, defined as the percentage difference between brain region volumes on each side.
Atrophy progression was measured as the percentage difference in volumes at follow-up versus baseline.
A statistical comparison of volumes at baseline and atrophy progression was performed using a two-sample t-test between MS patients with and without PIRA.
Results or Findings: We collected 95 MRIs from 40 patients with PIRA (26 with follow-up) and 55 patients without PIRA (43 with follow-up).
At baseline, the difference in asymmetry indices of total white matter, gray-matter occipital-lobe volume and parieto-occipital cortex volume were statistically significant (p<0.05): PIRA patients showed more right-side atrophy in the white matter volume and less in the right occipital lobe and parieto-occipital cortex than non-PIRA patients.
Atrophy progression was statistically different (p<0.05) for the gray-matter volume of the right temporal lobe, being faster in patients with PIRA than in those without (-3.1% vs -1.3%).
Conclusion: These results indicate that atrophy progression may be faster in MS patients with PIRA in regions related to early dementia and non-verbal language functions.
Limitations: Cohort size and statistical power show potential for improvement.
Funding for this study: No funding was received for this study.
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information: The study is retrospective.

Author Block: E. Lotan¹, V. Anania², T. Billiet², I. Kister¹, I. Lotan³; ¹New York, NY/US, ²Leuven/BE, ³Petach Tikva/IL
Purpose: Relatively little is known about how mean upper cervical cord area (MUCCA) changes in MOGAD compared to MS, NMOSD, and healthy controls (HC). We aim to assess MUCCA values in MOGAD as compared to MS, NMOSD, and HC.
Methods or Background: We retrospectively reviewed the NYU Multiple Sclerosis Care Center database to identify all adult MOGAD patients with available brain MRI performed in stable remission and compared them with NMOSD and MS patients and HC. Cross-sectional MUCCA from T1 brain MRIs was quantified using icobrain ms+ (version 5.15.0) and normalized for head size. A linear modeling analysis was used to evaluate the impact of covariates on cross-sectional MUCCA. The covariates were age, T1 slice-thickness, sex, and group. Post hoc testing was conducted using estimated marginal means (EMMEANS) to evaluate group differences while controlling for covariates.
Results or Findings: 20 MOGAD patients, 37 AQP4+ NMOSD patients, 40 MS patients, and 31 HC were included in the analysis. Age, sex, and group showed significant effects on MUCCA measurements. The EMMEANS of MUCCA values were lower for the NMOSD group (86.1+/-1.5), followed by MOGAD (89.3+/-1.7), MS (90.3+/-1.2), and HC (91.6+/-1.5). Pairwise comparison between groups showed no statistically significant differences between the MOGAD and other groups. In contrast, a statistically significant difference between the NMOSD and HC groups and a trend towards significance between the NMOSD and MS groups were observed.
Conclusion: Our proof of concept study shows the feasibility of calculating cervical volume loss from routine brain MRI using automated software. While greater spinal cord tissue loss is evident in NMOSD, the degree of spinal cord tissue loss in MOGAD is lower and not significantly different compared to MS and HC. Additional analyses on a larger cohort are underway.
Limitations: N/A
Funding for this study: No funding was provided for this study.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The ethics committee notification can be found under study number i20-01556

Author Block: W. H. E. Hamed, D. Werring, D. S Lynch, R. Jäger, T. A. Yousry; London/UK
Purpose: Evaluate the diagnostic utility of medial lemniscus (ML) in differentiating between multiple sclerosis (MS) and small vessel disease(SVD).
Methods or Background: Distinguishing between MS and SVD remains a significant challenge in the elderly due to their overlapping clinical presentations, emphasising the necessity for reliable, non-invasive neuroimaging markers such as ML.

A retrospective study analysed 270 MRI scans(100 MS, 170 SVD). SVD subtypes included arteriosclerotic(50), cerebral amyloid angiopathy(CAA)(50), mixed(50), and genetic(20). The signal intensity of ML in the pontine tegmentum was assessed visually on T2-w and FLAIR images. Statistical analysis included univariable tests to identify differences between MS and SVD, followed by multivariable logistic regression to determine independent predictors of ML involvement.
Results or Findings: SVD patients were significantly older than MS patients (mean age:68±13vs43±10 years, p<0.001) and had lower female predominance (44.7%vs64%). MS patients had no ML involvement(87%) or unilateral involvement(13%) with no bilateral cases, while 38% of SVD patients had bilateral involvement(p<0.001). Among SVD categories, ML involvement was most frequent in genetic(80%), followed by mixed(64%) and arteriosclerotic(46%). The least affected was CAA(20%).

In MS cohort, ML hyperintensity was associated with higher lesion load(p<0.001) but not the disease duration(p=0.4). Among SVD subtypes, the multivariable analysis revealed that lesion load(p<0.001) and hypertension(p=0.002) were the strongest predictors of ML involvement, followed by age(p=0.007), diabetes(p=0.023), and hypercholesterolemia(p=0.048). Factors such as alcohol, gender, and smoking were not significant predictors.
Conclusion: Our study establishes ML as a reliable radiological marker for distinguishing MS from SVD, particularly when there is bilateral involvement, evidenced by a statistically significant presence in SVD and a notable absence in MS. Moreover, the variation in ML involvement across SVD subtypes, specifically its minimal presence in pure CAA, suggests its potential role in differentiating specific SVD categories.
Limitations: Not applicable.
Funding for this study: No funding was provided for this study.
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information: A retrospective study

Author Block: S. Hannoun, S. Ghazal, L. Halawi, C. Al-Dahouk, N. El-Ayoubi, S. Khoury; Beirut/LB
Purpose: Differentiating patients who convert from relapsing-remitting Multiple sclerosis (RRMS) to secondary progressive MS (SPMS) remains a critical challenge, as early identification of converters can significantly impact treatment strategies. This study explores specific brain regions associated with disconnection probabilities and volume reductions, aiming to identify potential MRI biomarkers predictive of conversion. This study aimed to investigate whether distinct patterns of WM disconnection and regional brain atrophy are associated with RRMS conversion to SPMS.
Methods or Background: We retrospectively analyzed 47 RRMS patients (17 Converters and 30 non-converters) who underwent baseline and follow-up MRI scans approximately 1.5 years apart. Mixed-effects models evaluated the interaction between conversion status (converters vs. non-converters) and time across various brain regions, focusing on disconnection probabilities and volumetric changes measured using the Vol2Brain tool.
Results or Findings: Converters exhibited significant disconnection in key white matter tracts, including the uncinate fasciculus, corticobulbar tract, superior longitudinal fasciculus, and cingulum parahippocampal parietal. These disruptions are linked to cognitive, emotional, and motor functions. Additionally, grey matter atrophy was more pronounced in converters, particularly in the precentral gyrus, temporal lobe, and thalamus. Lesion burden and volume, especially in juxtacortical areas, were greater in converters, with increased third ventricle volume indicating more severe brain atrophy.
Conclusion: Specific patterns of white matter disconnection and regional brain atrophy are associated with conversion from RRMS to SPMS. These MRI biomarkers provide valuable insights into disease progression and offer potential therapeutic targets. Further validation in larger cohorts is needed to integrate these findings into clinical practice.
Limitations: A limitation of our study is its relatively small sample size and retrospective nature, which may limit the generalizability of the findings.
Funding for this study: No funding.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: This study was approved by the Institutional Review Board (IRB), and all participants provided informed consent.