Na Homolce Hospital

BackgroundIntramedullary melanocytoma of the spinal cord is an extremely rare primary melanocytic tumor, with less than 30 cases reported worldwide. Although histologically benign, these lesions may show locally aggressive behavior and a tendency for recurrence. We report an unprecedented case of multifocal intradural extramedullary recurrence following resection of an intramedullary melanocytoma, an occurrence not previously described in the English-language literature.Case presentationA 70-year-old woman presented with rapidly progressive weakness and sensory loss in both lower limbs. Four years earlier, she had undergone total resection of a histologically confirmed intramedullary melanocytoma of the conus medullaris. Current MRI revealed multiple intradural extramedullary lesions extending from the midthoracic to sacral levels, the largest at T5 and T11–T12, causing severe spinal cord compression. The lesions were hyperintense on T1-weighted, hypointense on T2-weighted and markedly hyperintense on T1 SPIR images, consistent with leptomeningeal dissemination of a melanocytic tumor. No intracranial lesions were detected. Given the extensive spinal involvement, further invasive diagnostics or radiotherapy were not indicated, and palliative management with corticosteroids and rehabilitation was initiated. The patient experienced gradual neurological deterioration with early spasticity and minimal partial recovery.ConclusionsThis case demonstrates that even histologically benign spinal melanocytomas can behave destructively and disseminate along the leptomeninges. Awareness of this potential, combined with long-term whole-neuraxis MRI surveillance, is crucial for early detection and timely management. The report highlights the unpredictable clinical course of these rare tumors and the need for individualized multidisciplinary care.

In patients with stable coronary artery disease (CAD), the long-term benefits of revascularization over medical therapy remain unclear. In the Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2 trial, patients with hemodynamically significant stenoses (fractional flow reserve (FFR) ≤ 0.80) were randomized to receive FFR-guided percutaneous coronary intervention (PCI) plus medical therapy (n = 447) or medical therapy alone (n = 441). At 5 years, FFR-guided PCI reduced the risk of the primary composite outcome of time to death, myocardial infarction or urgent revascularization, largely because of fewer urgent revascularizations. We now report the long-term clinical outcomes from this trial. Sixteen hospitals, contributing 748 randomized patients (161 women, 21.5%), participated in the long-term follow-up. The primary composite outcome was analyzed hierarchically using the unstratified win ratio, which addressed differential missingness of data on nonfatal outcomes in deceased patients by prioritizing comparisons on time to death. At a median follow-up of 11.2 years, the primary endpoint occurred in 150 of 447 patients (33.6%) in the PCI group versus 182 of 441 (41.3%) in the medical therapy group. PCI was superior in 29.2% of comparisons, medical therapy in 23.3%, and the two groups were tied in 47.5%, resulting in a win ratio of 1.25 in favor of PCI (95% confidence interval (CI) 1.01-1.56, P = 0.043). The corresponding win difference was 5.9% (95% CI 0.2-11.6), and the number needed to treat was 17 (95% CI 9-500). Win ratios were 0.88 for all-cause death (95% CI 0.66-1.17), 1.50 for myocardial infarction (95% CI 0.98-2.31) and 4.57 for urgent revascularization (95% CI 2.53-8.24). During long-term follow-up, FFR-guided PCI in patients with stable CAD and hemodynamically significant stenoses reduced the composite of death, myocardial infarction or urgent revascularization, primarily because of fewer urgent revascularizations. These long-term findings reaffirm the efficacy of FFR-guided PCI over medical therapy in patients with stable CAD. ClinicalTrials.gov registration: NCT06159231 .

Abstract BACKGROUND Astrocytoma, IDH-mutant, is the most common primary brain tumor in young adults, with peak incidence between 30 and 40 years of age. It is defined by mutations in the IDH1 or IDH2 genes and the absence of 1p/19q codeletion, and it frequently harbors alterations in ATRX and TP53. Rarely, astrocytoma, IDH-mutant, amay exhibit primitive neuronal differentiation, morphologically resembling “small round blue cell” tumors or large anaplastic embryonal-like cells. METHODS We analyzed 18 cases of astrocytoma, IDH-mutant, with primitive neuronal differentiation. In 11 cases where both the primitive neuronal and glial components were available, macrodissection was performed by a pathologist. Each component was subjected to separate genetic (next-generation sequencing) and epigenetic (DNA methylation profiling) analyses. Morphological and immunophenotypic features were also evaluated. RESULTS The primitive neuronal component was characterized by absent or markedly reduced GFAP expression, positivity for neuronal markers, a high Ki-67 proliferation index, and frequent TTF1 expression. This component also exhibited distinct epigenetic signatures and copy number alterations compared to the glial component. All tumors were high-grade, with extensive copy number variations, frequent MYCN amplification, and RB1 loss. DISCUSSION Astrocytoma, IDH-mutant, with a primitive neuronal component expands the morphological spectrum of IDH-mutant astrocytomas and presents a significant diagnostic challenge. Recognition of this rare subtype is critical due to its aggressive biological behavior. This work was supported by Masaryk University in Brno, Czech Republic, under Grant MUNI/A/1621/2024, the Ministry of Health, Czech Republic, grant project no. NU23-03-00100 and by the project National Institute for Cancer Research (Programme EXCELES, ID Project No. LX22NPO5102) - Funded by the European Union - Next Generation EU.

AimsThe feasibility and safety of the lattice-tip catheter for ventricular arrhythmia (VA) ablation in humans remain largely unknown. This study aimed to assess feasibility, safety profile as well as patient outcomes after VA ablation with a lattice-tip catheter in a multicentre European registry.Methods and resultsAll 18 European centres using the AFFERA system in September 2024 agreed to participate. Clinical, procedural, and follow-up data (minimum 3 months) were systematically collected and analysed. A total of 126 patients (18% female; mean age 59 ± 16 years) underwent VA ablation using the lattice-tip catheter during the inclusion period. Ablation indications included ventricular tachycardia (VT) in 99, premature ventricular complexes (PVCs) in 23, and ventricular fibrillation (VF) in 4 patients. Major and minor acute complications were observed in 7 (6%) and 18 (14%) procedures, respectively. They included thrombo-embolic event (n = 2), major bleeding (n = 2), ventricular fibrillation induction (n = 1), tamponade due to epicardial access (n = 1), and cardiogenic shock due to prolonged VT mapping (n = 1). Within the first month post-procedure, three patients died [from multi-organ failure (n = 2) and sepsis (n = 1)], two had worsening heart failure, one myocardial infarction, one sepsis, and one major gastro-intestinal bleeding. After a mean follow-up of 5.6 ± 3.7 months, absence of recurrence was 78% for PVC, 70% for VT, and 100% for VF.ConclusionIn this complex population with refractory VA, ablation using the lattice-tip catheter appears feasible and relatively safe. In the absence of large, randomized trials, exhaustive registry is of key importance to ensure safety and efficacy of new catheter technologies.

Diffusion tensor image analysis along the perivascular space (DTI-ALPS) is a potential non-invasive marker of glymphatic function that typically relies on manual region of interest (ROI) placement. This study compared ALPS indices in treatment-naïve, de novo diagnosed patients with Parkinson’s disease (PD), patients with isolated REM behavior disorder (iRBD), and healthy controls using both manual and automatic approaches to the ROI selection used in ALPS-index calculation. ALPS indices were analyzed bilaterally and correlated with clinical severity (MDS-UPDRS) and nigrostriatal denervation (DAT-SPECT). ANCOVA revealed significant inter-group differences using both manual (p = 0.018) and automatic (p = 0.002) ROI selection methods. The automatic ROI selection approach showed significantly lower ALPS indices in PD compared to controls (p = 0.001) and iRBD (p = 0.009). ALPS indices correlated with symptom severity and nigrostriatal denervation. These findings underscore the reliability of the automatic ROI placement approach for ALPS index calculation and may indicate early glymphatic alterations in Parkinson’s disease.

BackgroundKLOTHO-VS heterozygosity (KL-VSHET) and soluble α-Klotho (sαKl) protein interfere with Alzheimer's disease (AD) pathophysiology, but the specific relationships remain unclear. This study explored these associations across the AD continuum, focusing on core AD biomarkers and markers of neurodegeneration, neuroinflammation, and synaptic dysfunction.ObjectiveWe investigated whether 1) KL-VSHET is associated with lower AD biomarker burden (Aβ42, Aβ42/40 ratio, P-tau181, T-tau) and neurodegeneration (NfL); 2) sαKl relates to AD biomarkers, neurodegeneration (NfL), neuroinflammation (GFAP), and synaptic dysfunction (Ng); 3) associations vary by APOE ε4 status and clinical subgroup.MethodsParticipants (n = 223) were categorized as cognitively healthy (n = 38), aMCI-AD (n = 94), and AD dementia (n = 91). KLOTHO genotyping was available for 128 participants; 138 had cerebrospinal fluid (CSF) and serum sαKl measurements; and 42 had both. Multiple linear regression evaluated associations between KL-VSHET, sαKl levels, and biomarkers, stratified by APOE ε4 status and clinical subgroup.ResultsOverall, the associations between KL-VSHET and higher CSF Aβ42 and Aβ42/40 ratio were non-significant (ps ≥ 0.059) except when restricted to APOE ε4 carriers only (β = 0.11, p = 0.008 and β = 0.16, p = 0.033, respectively). Within clinical subgroups, KL-VSHET was positively associated with Aβ42/40 ratio only in aMCI-AD (β = 0.23, p = 0.034). No significant associations were observed between KL-VSHET and tau biomarkers or NfL. For sαKl, associations with biomarkers were non-significant except for a negative association of serum sαKl with P-tau181 in aMCI-AD (β = -0.25, p = 0.036) and a positive association with Aβ42/40 ratio in APOE ε4 non-carriers (β = 0.24 p = 0.047).ConclusionsKL-VSHET may help protect against amyloid pathology, particularly in the presence of APOE ε4, and regardless of APOE status in aMCI-AD.

Patients who experience seizures, including PNES, are usually advised to discontinue driving, or have their driving privileges revoked until a determined period of seizure-freedom is achieved. In this retrospective study, patients with PNES who requested driving privileges or reported having resumed driving were compared to those who did not on measures of depression, anxiety, PTSD, and cognitive flexibility/motor speed. DiagnosisofPNESwasconfirmedwithvideo-EEG.Demographicand clinical dataand requests for reinstatement of driving privileges (requiring 6 or more months seizure freedom) and reports of decisions to resume driving were noted. Tests of motor speed and hand eye coordination and self-report questionnaires of depression, anxiety and PTSD administered as part of neuropsychological assessment were analyzed. A total of 403 patients with PNES evaluated in 2010-2020 were identified. Of those, 365 patients were eligible for inclusion, and of those, 60 applied for driving privileges or reported that they resumed driving. When the two groups were compared, the group that applied for driving privileges or decided to resume driving was significantly less depressed (p=0.001) when tested than the group that did not. Furthermore, a significant difference was seen in measures of motor performance between those who requested to resume driving and those who did not (DKEFS T1, p=0.006, DKEFS T2, p=0.001, DKEFS T3, p=0.002, DKEFS T4, p=0.001; GPT dominant, p=0.05, GPT non-dominant, p=0.003). Driving a motor vehicle is a useful measure of improvement for PNES because patients with seizures are required to discontinue driving until seizure-freedom is achieved. This study revealed that lower levels of depression and better fine motor functioning were associated with reported seizure-freedom and driving resumption. Depression is commonly associated with diminished performance (slower motor response times and impaired fine motor movements) on tests of motor functioning, both of which may result in less interest in pursuing permission to resume driving. These findings suggest that mood symptoms (and associated performance on measures of motor speed and coordination) may have prognostic significance in patients diagnosed with PNES. This also suggests that timely treatment of depression in newly diagnosed patients with PNES may be indicated.