OBJECTIVE: We comprehensively characterized a large pediatric cohort with focal cortical dysplasia (FCD) type 1 to expand the phenotypic spectrum and to identify predictors of postsurgical outcomes. METHODS: We included pediatric patients with histopathological diagnosis of isolated FCD type 1 and at least 1 year of postsurgical follow-up. We systematically reanalyzed clinical, electrophysiological, and radiological features. The results of this reanalysis served as independent variables for subsequent statistical analyses of outcome predictors. RESULTS: All children (N = 31) had drug-resistant epilepsy with varying impacts on neurodevelopment and cognition (presurgical intelligence quotient [IQ]/developmental quotient scores = 32-106). Low presurgical IQ was associated with abnormal slow background electroencephalographic (EEG) activity and disrupted sleep architecture. Scalp EEG showed predominantly multiregional and often bilateral epileptiform activity. Advanced epilepsy magnetic resonance imaging (MRI) protocols identified FCD-specific features in 74.2% of patients (23/31), 17 of whom were initially evaluated as MRI-negative. In six of eight MRI-negative cases, fluorodeoxyglucose-positron emission tomography (PET) and subtraction ictal single photon emission computed tomography coregistered to MRI helped localize the dysplastic cortex. Sixteen patients (51.6%) underwent invasive EEG. By the last follow-up (median = 5 years, interquartile range = 3.3-9 years), seizure freedom was achieved in 71% of patients (22/31), including seven of eight MRI-negative patients. Antiseizure medications were reduced in 21 patients, with complete withdrawal in six. Seizure outcome was predicted by a combination of the following descriptors: age at epilepsy onset, epilepsy duration, long-term invasive EEG, and specific MRI and PET findings. SIGNIFICANCE: This study highlights the broad phenotypic spectrum of FCD type 1, which spans far beyond the narrow descriptions of previous studies. The applied multilayered presurgical approach helped localize the epileptogenic zone in many previously nonlesional cases, resulting in improved postsurgical seizure outcomes, which are more favorable than previously reported for FCD type 1 patients.

• MeSH
• Child MeSH
• Electroencephalography * methods   MeSH
• Epilepsy MeSH
• Focal Cortical Dysplasia MeSH
• Cohort Studies MeSH
• Infant MeSH
• Humans MeSH
• Magnetic Resonance Imaging * MeSH
• Malformations of Cortical Development, Group I * surgery   complications   diagnostic imaging   MeSH
• Malformations of Cortical Development surgery   complications   diagnostic imaging   MeSH
• Adolescent MeSH
• Positron-Emission Tomography MeSH
• Child, Preschool MeSH
• Drug Resistant Epilepsy * surgery   diagnostic imaging   physiopathology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Limited licensed medications are available for multiple sclerosis (MS) in pediatric patients. OBJECTIVE: To evaluate the efficacy, safety, and tolerability of alemtuzumab in pediatric patients with relapsing-remitting multiple sclerosis (RRMS) and disease activity on prior disease-modifying therapies (DMTs). METHODS: LemKids was a multicenter, multinational, single-arm, open-label, switch (from ongoing DMT to alemtuzumab treatment) study in pediatric RRMS patients (aged 10-<18 years), with disease activity on DMT. The primary endpoint was a comparison of the number of new/enlarging T2 lesions on the magnetic resonance imaging of the brain between the prior-DMT period and alemtuzumab treatment. RESULTS: This study was prematurely terminated due to low enrollment and an European Medicines Agency Article-20 pharmacovigilance review of alemtuzumab in adult RRMS. Of 46 screened patients, 16 were enrolled; 12 completed prior-DMT treatment period; 11 received alemtuzumab of whom 7 completed treatment. Patients on alemtuzumab developed fewer new/enlarging T2 lesions compared with prior-DMT (7 vs 178, relative risk (95% confidence interval): 0.04 (0.01-0.14)). No significant pharmacodynamic changes or safety concerns were noted in this limited dataset. CONCLUSION: Alemtuzumab treatment was associated with a low number of new/enlarging T2 lesions in pediatric patients with RRMS and was safe and well tolerated in seven patients during infusion and the initial 4 months.

• MeSH
• Alemtuzumab * adverse effects   MeSH
• Child MeSH
• Immunologic Factors * adverse effects   administration & dosage   MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Adolescent MeSH
• Multiple Sclerosis, Relapsing-Remitting * drug therapy   diagnostic imaging   MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

BACKGROUND: Modafinil is primarily used to treat narcolepsy but is also used as an off-label cognitive enhancer. Functional magnetic resonance imaging studies indicate that modafinil modulates the connectivity of neocortical networks primarily involved in attention and executive functions. However, much less is known about the drug's effects on subcortical structures. Following preliminary findings, we evaluated modafinil's activity on the connectivity of distinct cerebellar regions with the neocortex. We assessed the spatial relationship of these effects with the expression of neurotransmitter receptors/transporters. METHODS: Patterns of resting-state functional magnetic resonance imaging connectivity were estimated in 50 participants from scans acquired pre- and postadministration of a single (100 mg) dose of modafinil (n = 25) or placebo (n = 25). Using specific cerebellar regions as seeds for voxelwise analyses, we examined modafinil's modulation of cerebellar-neocortical connectivity. Next, we conducted a quantitative evaluation of the spatial overlap between the modulation of cerebellar-neocortical connectivity and the expression of neurotransmitter receptors/transporters obtained by publicly available databases. RESULTS: Modafinil increased the connectivity of crus I and vermis IX with prefrontal regions. Crus I connectivity changes were associated with the expression of dopaminergic D2 receptors. The vermis I-II showed enhanced coupling with the dorsal anterior cingulate cortex and matched the expression of histaminergic H3 receptors. The vermis VII-VIII displayed increased connectivity with the visual cortex, an activity associated with dopaminergic and histaminergic neurotransmission. CONCLUSIONS: Our study reveals modafinil's modulatory effects on cerebellar-neocortical connectivity. The modulation mainly involves crus I and the vermis and spatially overlaps the distribution of dopaminergic and histaminergic receptors.

• MeSH
• Adult MeSH
• Humans MeSH
• Magnetic Resonance Imaging * MeSH
• Young Adult MeSH
• Modafinil * pharmacology   administration & dosage   MeSH
• Cerebellum * drug effects   diagnostic imaging   metabolism   MeSH
• Neocortex drug effects   metabolism   diagnostic imaging   MeSH
• Neural Pathways drug effects   metabolism   MeSH
• Wakefulness-Promoting Agents pharmacology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH

OBJECTIVE: Research suggests that disrupted interoception contributes to the development and maintenance of functional neurological disorder (FND); however, no functional neuroimaging studies have examined the processing of interoceptive signals in patients with FND. METHODS: The authors examined univariate and multivariate functional MRI neural responses of 38 patients with mixed FND and 38 healthy control individuals (HCs) during a task exploring goal-directed attention to cardiac interoception-versus-control (exteroception or rest) conditions. The relationships between interoception-related neural responses, heartbeat-counting accuracy, and interoceptive trait prediction error (ITPE) were also investigated for FND patients. RESULTS: When attention was directed to heartbeat signals versus exteroception or rest tasks, FND patients showed decreased neural activations (and reduced coactivations) in the right anterior insula and bilateral dorsal anterior cingulate cortices (among other areas), compared with HCs. For FND patients, heartbeat-counting accuracy was positively correlated with right anterior insula and ventromedial prefrontal activations during interoception versus rest. Cardiac interoceptive accuracy was also correlated with bilateral dorsal anterior cingulate activations in the interoception-versus-exteroception contrast, and neural activations were correlated with ITPE scores, showing inverse relationships to those observed for heartbeat-counting accuracy. CONCLUSIONS: This study identified state and trait interoceptive disruptions in FND patients. Convergent between- and within-group findings contextualize the pathophysiological role of cingulo-insular (salience network) areas across the spectrum of functional seizures and functional movement disorder. These findings provide a starting point for the future development of comprehensive neurophysiological assessments of interoception for FND patients, features that also warrant research as potential prognostic and monitoring biomarkers.

• MeSH
• Adult MeSH
• Interoception * physiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Brain Mapping MeSH
• Young Adult MeSH
• Brain * physiopathology   diagnostic imaging   MeSH
• Nervous System Diseases * physiopathology   diagnostic imaging   MeSH
• Attention physiology   MeSH
• Heart Rate physiology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Cíl: 18 F-fluorestradiol je nové radiofarmakum, které lze použít při zobrazování karcinomu prsu, indikace v klinických postupech ještě nemají své pevné místo, proto je cílem studie posoudit klinický význam zobrazení karcinomu prsu estrogen-pozitivních receptorů (ER+) pomocí 18 F-fluorestradiolu (18 F-FES) PET/CT nebo PET/MR z hlediska využití při rozhodnutí o léčbě. Studie se zabývá také volbou využití PET/CT nebo PET/MR ve stagingu a restagingu karcinomu prsu. Metodika: U 40 pacientek s estrogen pozitivním karcinomem prsu bylo provedeno hybridní zobrazení s intravenózní aplikací 18 F-FES, ve 25 případech bylo použito PET/CT, v 15 případech PET/MR. Radiofarmakum bylo injekčně aplikováno v aktivitě 2,5 MBq/kg. U deseti pacientek byla jako restagingová metoda použito PET/ MR, v pěti případech stagingu před operací bylo provedeno PET/MR s cíleným plným diagnostickým MR zobrazením prsu v pronační poloze s následným zobrazením trupu v poloze na zádech. Všechna vyšetření PET/MR byla provedena po aplikaci gadoliniové kontrastní látky, zobrazení zahrnovalo zobrazení mozku v T1 STARVIBE. PET/CT bylo provedeno kontinuální PET akvizicí následně po akvizici CT s intravenózním podáním jodované kontrastní látky, v pěti případech bylo provedeno ve stagingu, ve 20 případech v restagingu. Výsledky: Nejdůležitějším výsledkem byla detekce ER+ metastáz při negativním výsledku 18 F-FDG-PET (12krát) – včetně mozkových a jaterních metastáz, perzistující ER+ metastáz (7krát), staging onemocnění (10krát), ztráta ER (4krát) a negativní nález pro metastázy (2), při pěti vyšetřeních nebyly nalezeny žádné přidané informace. Závěr: 18 F-FES-PET poskytuje klinicky vý- znamné informace pro volbu léčebné strategie, 18 F-FES-PET/MR je výhodné vyšetření při zaměření na zobrazení mozku a jater s možnos- tí prokázat anebo vyloučit metastázy v těchto orgánech.

Aim. 18 F-fluoroestradiol is a novel radiopharmaceutical useful in the imaging of breast carcinoma, the indications in clinical scenarios are under development. The purpose of the study is to assess the clinical impact of the imaging of the breast carcinoma with estrogenpositive receptors (ER+) using 18 F-fluoroestra- diol ( 18 F-FES) PET/CT or PET/MRI according to the treatment decision making. The study is concerned in the different preference of PET/CT and PET/MRI in the staging and restaging. Methods. 40 patients with estrogen positive breast carcinoma underwent the hybrid imaging after intravenous application of 18 F-FES, in 25 cases it was used PET/CT, in 15 cases PET/ MRI. The radiopharmaceutical was injected with the activity of 2,5 MBq/kg. In 10 patient, PET/MRI was used as restaging method, PET/ MRI was performed in the 5 cases of the staging before surgery with targeted full diagnostic MRI imaging of the breast in prone position, followed by the trunk imaging in supine position. All PET/MRI were performed after application of the gadolinium contrast material, the imaging included brain imaging in T1 STARVIBE. PET/CT was performed using the continuous PET acquisition after CT with the intravenous administration of the iodinated contrast material, in 5 cases was performed in staging, in 20 cases in restaging Results. The most important informa- tion was detection of ER+ metastases when 18 F-FDG-PET was negative (12×) – including brain and liver metastases, the persistent ER+ of the metastases (7×), staging of the disease (10×), the loss of the ER (4x) and the negative finding for metastases (2), no added information was found in 5 examinations. Conclusion. 18 F-FES-PET provided the impor- tant clinical information to treatment strategy, 18 F-FES-PET/MRI improves the imaging of metastases in brain and liver.

The study evaluates the efficacy of RETROICOR (Retrospective Image Correction) in mitigating physiological artifacts within multi-echo (ME) fMRI data. Two RETROICOR implementations were compared: applying corrections to individual echoes (RTC_ind) versus composite multi-echo data (RTC_comp). Data from 50 healthy participants were collected using diverse acquisition parameters, including multiband acceleration factors and varying flip angles, on a Siemens Prisma 3T scanner. Key metrics such as temporal signal-to-noise ratio (tSNR), signal fluctuation sensitivity (SFS), and variance of residuals demonstrated improved data quality in both RETROICOR models, particularly in moderately accelerated runs (multiband factors 4 and 6) with lower flip angles (45°). Differences between RTC_ind and RTC_comp were minimal, suggesting both methods are viable for practical applications. While the highest acceleration (multiband factor 8) degraded data quality, RETROICOR's compatibility with faster acquisition sequences was confirmed. These findings underscore the importance of optimizing acquisition parameters and noise correction techniques for reliable fMRI investigations.

• MeSH
• Artifacts * MeSH
• Adult MeSH
• Humans MeSH
• Magnetic Resonance Imaging * methods   MeSH
• Brain Mapping * methods   MeSH
• Young Adult MeSH
• Brain * diagnostic imaging   physiology   MeSH
• Image Processing, Computer-Assisted * methods   MeSH
• Signal-To-Noise Ratio MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND AND AIMS: Anti-tumor necrosis factor-α inhibitors (anti-TNFs) are the established treatment for perianal Crohn's disease (pCD), but relapse and non-response are common. Data on second- and third-line biologics are limited. We present the first direct comparison of second- and third-line biologics in pCD patients with active perianal disease previously treated with first-line anti-TNFs. METHODS: A multicenter retrospective cohort study included adult patients with pCD who failed first-line anti-TNF. The primary outcome was clinical perianal response, with secondary outcomes of radiological response (magnetic resonance imaging or transrectal ultrasound) and healing, and clinical remission. Propensity score matching (PSM) was used to adjust for baseline differences. RESULTS: A total of 486 pCD patients from 23 IBD centers were included, with 333/486 (68.5%) and 216/263 (82.1%) matched by PSM in the second and third-line treatment groups, respectively. In the second-line group, 62/78 (79.5%) of ustekinumab (UST)-treated patients achieved clinical perianal response, compared to 46/78 (58.9%) with vedolizumab (VDZ) (OR 4.47, 95% CI, 1.94-10.28, P < .001) and 38/78 (48.7%) with anti-TNFs (OR 5.29, 95% CI, 2.39-11.71, P < .001). In the third-line group, 38/49 (77.6%) of UST-treated patients achieved clinical perianal response, compared to 29/49 (59.2%) with VDZ (OR 9.96, 95% CI, 2.6-38.4, P < .001) and 27/49 (55.1%) with anti-TNFs (OR 12.03, 95% CI, 2.99-48.47, P < .001). UST-treated patients also had higher radiological response rates than VDZ (OR 3.28, 95% CI, 1.07-10.07, P = .038). CONCLUSION: In pCD patients failing anti-TNFs as first-line treatment, ustekinumab may be more effective than vedolizumab or another anti-TNF as second or third-line therapy.

• MeSH
• Biological Products * therapeutic use   MeSH
• Crohn Disease * drug therapy   diagnostic imaging   MeSH
• Adult MeSH
• Gastrointestinal Agents * therapeutic use   MeSH
• Antibodies, Monoclonal, Humanized therapeutic use   MeSH
• Remission Induction MeSH
• Tumor Necrosis Factor Inhibitors therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Anus Diseases * drug therapy   MeSH
• Retrospective Studies MeSH
• Propensity Score MeSH
• Ustekinumab * therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Tools for post-operative localization of deep brain stimulation (DBS) electrodes may be of major benefit in the evaluation of the stimulation area. However, little is known about their precision. This study compares 3 different software packages used for DBS electrode localization. T1-weighted MRI images before and after the implantation of the electrodes into the subthalamic nucleus for DBS in 105 Parkinson's disease patients were processed using the pipelines implemented in Lead-DBS, SureTune4, and Brainlab. Euclidean distance between active contacts determined by individual software packages and in repeated processing by the same and by a different operator was calculated. Furthermore, Dice coefficient for overlap of volume of tissue activated (VTA) was determined for Lead-DBS. Medians of Euclidean distances between estimated active contact locations in inter-software package comparison ranged between 1.5 mm and 2 mm. Euclidean distances in within-software package intra- and inter-rater assessments were 0.6-1 mm and 1-1.7 mm, respectively. Median intra- and inter-rater Dice coefficients for VTAs were 0.78 and 0.75, respectively. Since the median distances are close to the size of the target nucleus, any clinical use should be preceded by careful review of the outputs.

• MeSH
• Deep Brain Stimulation * methods   instrumentation   MeSH
• Electrodes, Implanted * MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Subthalamic Nucleus surgery   MeSH
• Parkinson Disease * therapy   MeSH
• Aged MeSH
• Software MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system (CNS), characterized by inflammation and neurodegeneration. The pathophysiology of MS, especially its progressive forms, involves various cellular components, including microglia, the primary resident immune cells of the CNS. This review discusses the role of microglia in neuroinflammation, tissue repair, and neural homeostasis, as well as their involvement in MS and explores potential therapeutic strategies targeting microglial function. METHODS: A literature search conducted in August 2023 and updated in March 2025, using the PubMed database, focused on articles relating to microglia and MS published in 2018-2025. Additionally, ongoing clinical trials of Bruton's tyrosine kinase (BTK) inhibitors were identified through the ClinicalTrials.gov website in November 2023 and updated in March 2025. RESULTS: Microglia are highly adaptive and exhibit various functional states throughout different life stages and play critical roles in neuroinflammation, tissue repair, and neural homeostasis. Their altered activity is a prominent feature of MS, contributing to its pathogenesis. Imaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) provide insights into microglial activity in MS. BTK inhibitors and other novel treatments for MS, including masitinib and frexalimab, show promise in modulating microglial function and influencing the disease progression rate. CONCLUSIONS: The multifaceted roles of microglia in CNS development, immune surveillance, and particularly in the pathogenesis of MS highlight the potential of targeting microglial functions in MS treatment. Emerging research on the involvement of microglia in MS pathophysiology offers promising avenues for developing novel therapies, especially for progressive MS, potentially improving patient outcomes in this debilitating disease.

• MeSH
• Protein Kinase Inhibitors * therapeutic use   pharmacology   MeSH
• Tyrosine Kinase Inhibitors MeSH
• Humans MeSH
• Microglia * drug effects   immunology   metabolism   MeSH
• Agammaglobulinaemia Tyrosine Kinase * antagonists & inhibitors   metabolism   MeSH
• Multiple Sclerosis * drug therapy   immunology   etiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

The aim of this study was to test the hypothesis that individuals with an increase in HbA1c (i.e. above the regular but below the diabetic threshold) exhibit an impairment in the Achilles tendon structure and walking capacity, due to the adverse effect of the advanced glycation end-product. One hundred fifty-eight participants matched for gender, age, physical activity and BMI, were divided in two cohorts based on the HbA1c level: normal HbA1c (NGH; <39 mmol/molHb; n = 79) and altered HbA1c (AGH; >=39 mmol/molHb; n = 79). Each participant performed several walking trials to evaluate the kinematic parameters during walling at the self-selected speed and a quantitative MRI scan of the Achilles tendon (AT) to obtain its intrinsic characteristics (i.e. T2* relaxation time short and long component). The AT T2* relaxation time short component (a parameter related to the tendon collagen quality) was reduced in AGH compared to NGH. Furthermore, AGH exhibited a slower self-selected walking speed (NGH: 1.59 ± 0.18 m/s; AGH:1.54 ± 0.16 m/s) and a shorter stride length (NGH: 1.59 ± 0.13 m; AGH:1.55 ± 0.11 m). Our data suggest that a non-pathological increase in HbA1c is able to negatively affect AT collagen quality and walking capacity in healthy people. These results highlight the importance of glycemic control, even below the pathological threshold. Since diabetes could alter several biological pathways, further studies are necessary to determine which mechanisms and their timing, regarding the HbA1c rise, affect tendon composition and, consequently, walking capacity.

• MeSH
• Achilles Tendon * diagnostic imaging   physiology   metabolism   MeSH
• Biomechanical Phenomena MeSH
• Walking * physiology   MeSH
• Diabetes Mellitus diagnosis   MeSH
• Adult MeSH
• Glycated Hemoglobin * metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Glycation End Products, Advanced metabolism   MeSH
• Healthy Volunteers MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH