In current international classification systems (ICD-10, DSM5), the diagnostic criteria for psychotic disorders (e.g. schizophrenia and schizoaffective disorder) are based on symptomatic descriptions ...since no unambiguous biomarkers are known to date. However, when underlying causes of psychotic symptoms, like inflammation, ischemia, or tumor affecting the neural tissue can be identified, a different classification is used ("psychotic disorder with delusions due to known physiological condition" (ICD-10: F06.2) or psychosis caused by medical factors (DSM5)). While CSF analysis still is considered optional in current diagnostic guidelines for psychotic disorders, CSF biomarkers could help to identify known physiological conditions. In this retrospective, partly descriptive analysis of 144 patients with psychotic symptoms and available CSF data, we analyzed CSF examinations' significance to differentiate patients with specific etiological factors (F06.2) from patients with schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders (F2). In 40.3% of all patients, at least one CSF parameter was out of the reference range. Abnormal CSF-findings were found significantly more often in patients diagnosed with F06.2 (88.2%) as compared to patients diagnosed with F2 (23.8%, p < 0.00001). A total of 17 cases were identified as probably caused by specific etiological factors (F06.2), of which ten cases fulfilled the criteria for a probable autoimmune psychosis linked to the following autoantibodies: amphiphysin, CASPR2, CV2, LGl1, NMDA, zic4, and titin. Two cases presented with anti-thyroid tissue autoantibodies. In four cases, further probable causal factors were identified: COVID-19, a frontal intracranial tumor, multiple sclerosis (n = 2), and neurosyphilis. Twenty-one cases remained with "no reliable diagnostic classification". Age at onset of psychotic symptoms differed between patients diagnosed with F2 and F06.2 (p = 0.014), with the latter group being older (median: 44 vs. 28 years). Various CSF parameters were analyzed in an exploratory analysis, identifying pleocytosis and oligoclonal bands (OCBs) as discriminators (F06.2 vs. F2) with a high specificity of > 96% each. No group differences were found for gender, characteristics of psychotic symptoms, substance dependency, or family history. This study emphasizes the great importance of a detailed diagnostic workup in diagnosing psychotic disorders, including CSF analysis, to detect possible underlying pathologies and improve treatment decisions.
Within the past 10 years, immune mechanisms associated with acute ischemic stroke (AIS) have been brought into focus, but data on B cell activation and intrathecal Ig production is still scarce. In ...this study, we determined the prevalence of an elevated IgG index, positive oligoclonal bands (OCBs) and chemokine C-X-C motif ligand 13 (CXCL13) levels in the cerebrospinal fluid (CSF) as markers of intrathecal IgG synthesis and B cell activation in patients with AIS.
In a retrospective study we analyzed the cerebrospinal fluid (CSF) from 212 patients with AIS from December 2013 to May 2018 assessing intrathecal Ig synthesis, OCBs and CXCL13 concentrations.
Overall, 5.7% (12/212) of AIS patients showed an intrathecal IgG synthesis, 0.5% (1/212) with isolated elevated IgG index, 5.2% (7/136) isolated positive OCBs and 2.9% (4/136) both elevated IgG index and positive OCBs. CXCL13 levels were elevated in 3.6% (3/83) of the patients. Approximately one third of these patients had simultaneously chronic inflammatory CNS disease (multiple sclerosis, neuromyelitis optica spectrum disorder, neurosarcoidosis). There was no significant association between CSF findings and stroke characteristics including vascular territory, localization, volume, etiology, acute treatment, or blood-brain barrier dysfunction. Intrathecal IgG synthesis was more common in patients with prior stroke. Longitudinal CSF analysis did not reveal any newly-occurring, but instead mostly persistent or even disappearing intrathecal IgG synthesis after AIS.
We found no evidence of a relevant B cell recruitment and intrathecal IgG synthesis in patients with AIS. In fact, the occurrence of intrathecal IgG synthesis was associated with concurrent chronic inflammatory CNS disease or previous stroke. Consequently, in patients with first-ever AIS and intrathecal IgG synthesis, physicians should search for concomitant inflammatory CNS disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A fully diagnostic MRI glioma protocol is key to monitoring therapy assessment but is time-consuming and especially challenging in critically ill and uncooperative patients. Artificial intelligence ...demonstrated promise in reducing scan time and improving image quality simultaneously. The purpose of this study was to investigate the diagnostic performance, the impact on acquisition acceleration, and the image quality of a deep learning optimized glioma protocol of the brain. Thirty-three patients with histologically confirmed glioblastoma underwent standardized brain tumor imaging according to the glioma consensus recommendations on a 3-Tesla MRI scanner. Conventional and deep learning-reconstructed (DLR) fluid-attenuated inversion recovery, and T2- and T1-weighted contrast-enhanced Turbo spin echo images with an improved in-plane resolution, i.e., super-resolution, were acquired. Two experienced neuroradiologists independently evaluated the image datasets for subjective image quality, diagnostic confidence, tumor conspicuity, noise levels, artifacts, and sharpness. In addition, the tumor volume was measured in the image datasets according to Response Assessment in Neuro-Oncology (RANO) 2.0, as well as compared between both imaging techniques, and various clinical-pathological parameters were determined. The average time saving of DLR sequences was 30% per MRI sequence. Simultaneously, DLR sequences showed superior overall image quality (all
< 0.001), improved tumor conspicuity and image sharpness (all
< 0.001, respectively), and less image noise (all
< 0.001), while maintaining diagnostic confidence (all
> 0.05), compared to conventional images. Regarding RANO 2.0, the volume of non-enhancing non-target lesions (
= 0.963), enhancing target lesions (
= 0.993), and enhancing non-target lesions (
= 0.951) did not differ between reconstruction types. The feasibility of the deep learning-optimized glioma protocol was demonstrated with a 30% reduction in acquisition time on average and an increased in-plane resolution. The evaluated DLR sequences improved subjective image quality and maintained diagnostic accuracy in tumor detection and tumor classification according to RANO 2.0.
: Immune checkpoint inhibitors (ICIs) have enriched tumor therapy, improving overall survival. Immunotherapy adverse events (irAEs) occur in up to 50% of patients and also affect the peripheral ...nervous system. The exact pathomechanism is unclear; however, an autoimmune process is implicated. Thus, the clinical evaluation of irAEs in the peripheral nervous system is still demanding. We retrospectively analyzed nerve ultrasound (NU) data of polyneuropathies (PNPs) secondary to checkpoint inhibitors.
: NU data of patients with PNP symptoms secondary to ICI therapy were retrospectively analyzed using the Ultrasound Pattern Sum Score (UPSS) as a quantitative marker. Our findings were compared with a propensity score match analysis (1:1 ratio) to NU findings in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and chemotherapy-associated PNP patients.
: In total, 10 patients were included (4 female, mean age 66 ± 10.5, IQR 60-77), where NU was performed in 80%. The UPSS obtained ranged from 0 to 5 (mean 2 ± 1.6, IQR 1-2.5). The morphological changes seen in the NUs resembled sonographic changes seen in chemotherapy-associated PNP (n = 10, mean UPSS 1 ± 1, IQR 0-2) with little to no nerve swelling. In contrast, CIDP patients had a significantly higher UPSS (n = 10, mean UPSS 11 ± 4, IQR 8-13,
< 0.0001).
: Although an autoimmune process is hypothesized to cause peripheral neurological irAEs, NU showed no increased swelling as seen in CIDP. The nerve swelling observed was mild and comparable to ultrasound findings seen in chemotherapy-associated PNP.
Direct oral anticoagulants (DOAC) including edoxaban are increasingly used for stroke prevention in atrial fibrillation. Despite treatment, annual stroke rate in these patients remains 1-2%. Rapid ...assessment of coagulation would be useful to guide thrombolysis or reversal therapy in this growing population of DOAC/edoxaban-treated stroke patients. Employing the Hemochron™ Signature Elite point-of-care test system (HC-POCT), clinically relevant plasma concentrations of dabigatran and rivaroxaban can be excluded in a blood sample. However, no data exists on the effect of edoxaban on HC-POCT results. We evaluated whether edoxaban plasma concentrations above the current treatment thresholds for thrombolysis or anticoagulation reversal (i.e., 30 and 50 ng/mL) can be ruled out with the HC-POCT.
We prospectively studied patients receiving a first dose of edoxaban. Six blood samples were collected from each patient: before, 0.5, 1, 2, 8, and 24 h after drug intake. HC-POCT-based INR (HC-INR), activated clotting time (HC-ACT+ and HC-ACT-LR), activated partial thromboplastin time (HC-aPTT), and mass spectrometry for edoxaban plasma concentrations were performed at each time-point. We calculated correlations, receiver operating characteristics (ROC) and test-specific cut-offs for ruling out edoxaban concentrations > 30 and > 50 ng/mL in a blood sample.
One hundred twenty blood samples from 20 edoxaban-treated patients were analyzed. Edoxaban plasma concentrations ranged from 0 to 512 ng/mL. HC-INR/HC-ACT+/HC-ACT-LR/HC-aPTT ranged from 0.7-8.3/78-310 s/65-215 s/19-93 s, and Pearson's correlation coefficients showed moderate to very strong correlations with edoxaban concentrations (r = 0.95/0.79/0.70/0.60). With areas under the ROC curve of 0.997 (95% confidence interval: 0.991-0.971) and 0.989 (0.975-1.000), HC-INR most reliably ruled out edoxaban concentrations > 30 and > 50 ng/mL, respectively, and HC-INR results ≤1.5 and ≤ 2.1 provided specificity/sensitivity of 98.6% (91.2-99.9)/98.0% (88.0-99.9) and 96.8% (88.0-99.4)/96.5% (86.8-99.4).
Our study represents the first systematic evaluation of the HC-POCT in edoxaban-treated patients. Applying sufficiently low assay-specific cut-offs, the HC-POCT may not only be used to reliably rule out dabigatran and rivaroxaban, but also very low edoxaban concentrations in a blood sample. Because the assay-specific cut-offs were retrospectively defined, further investigation is warranted.
ClinicalTrials.gov, registration number: NCT02825394 , registered on: 07/07/2016, URL.
A 61-year-old patient was diagnosed with a left-sided falx meningioma. Histopathological analysis following extirpation showed a meningothelial meningioma ZNS WHO grade 1 with sparse mitoses. Over ...the course of 12 years, the patient received irradiation (54.0 Gy), peptide radio-receptor therapy (
Lu-DOMITATE) and targeted therapy (mTOR inhibitor). Follow-up imaging revealed an increased size of the residual tumor. Due to increased liver function parameters, imaging of the liver was performed, showing widespread space-occupying lesions with atypical appearance. Biopsy revealed metastasis of the meningioma, now with 2.7 mitoses/mm
, necrosis and homozygous CDKN2A/B deletion, corresponding to an anaplastic CNS meningioma WHO grade 3. A second small meningioma on the left petroclival side has been consistent in size over 12 years. Metastatic meningiomas pose a pertinent clinical challenge due to poor prognosis. The lung, bone, liver and cervical lymph nodes are the most common sites of extracranial metastasis. According to the World Health Organization criteria, the most important predictive factor for recurrence and metastasis is the tumor grade.
Abstract
OBJECTIVE
The diagnosis of a brain tumor represents high burden for the patients’ caregivers (CG). Psychosocial screening tools adapted to the burden profile of CG are urgently required but ...do not exist. The aim was to develop a problem list for neuro-oncological CGs’ unmet needs for an application in combination to the Distress Thermometer scale.
METHODS
CG were prospectively assessed regarding changes in everyday life, relationship, social life, emotional, physical problems, and support needs, either via questionnaire (Center A) or by a qualitative interview (center B). A qualitative content analysis was performed by an inductive/deductive approach using MAXQDA® software.
RESULTS
A total of 50 caregivers were assessed (25 in center A via questionnaire, 25 in center B via interviews) during outpatient visits. Most frequently reported need was the need for psychological support (29/50, 58%). This was true after initial diagnosis (26/50, 52%) as well as in case of clinical deterioration of their loved-one (30/50, 60%). The results leaded to problem categories, congruent to the NCCN distress thermometer categories for cancer patients (practical, social, emotional, physical, and spiritual/existential problems). We detected new topics including “constraints/organization of (medical) appointments” (25/50, 50%) or “constant availability required for partner” (21/50, 42%). Also, 70% (35/50) put their own interests last or adapted their leisure activities. In the qualitative interviews (Center B), further items were identified, e.g., “dealing with psychological problems of the patient” (3/25, 12%), “different coping strategies among patient/caregiver” (4/25, 16%). We defined additional problem categories specifically adapted to CG of neurooncological patients, e.g., “problems due to neurocognitive/neuropsychological symptoms of the loved-one” and “problems with role as a caregiver”.
CONCLUSION
The interviews reflected the unmet needs of brain tumor caregivers. Our problem list developed for CG of neurooncological patients might allow for the targeted assessment and optimization of care.
Abstract
BACKGROUND
Once first-line therapy options fail, there are no effective therapy options for most neuro-oncological conditions, including glioblastoma, gliomas, and brain metastases, thereby ...representing a high unmet clinical need. Novel targeted therapy options are often explored in small phase-I studies or are given as off-label therapies. Assessment of treatment efficacy in this setting is challenging and should incorporate outcome measures such as progression-free survival (PFS) or objective response rate (ORR) as well as clinical parameters. To address this, we developed the Neuro-Oncology Magnitude of Clinical Benefit Scale (Neuro-MCBS) as a comprehensive clinical tool to assess treatment efficacy in patients with CNS tumors who receive off-label targeted therapies outside of clinical trials. We prospectively evaluated the feasibility and clinical utility of the Neuro MCBS in a neuro-oncology patient cohort enrolled in MTB@ZPM.
METHODS
MTB@ZPM (NCT03503149) is a longitudinal observational study that provides comprehensive molecular profiling, consensus-guided and ranked targeted therapy recommendations and collection of prospective clinical outcome data. The Neuro-MCBS (grade 1 + 2=clinical benefit, grade 3=minimal benefit, grade 0=no benefit) was applied and correlated with PFS, the PFS2/PFS1 ratio, performance status (KPS, ECOG), and imaging parameters.
RESULTS
From February 1st, 2022 until January 31st, 2023, 70 patients were enrolled. While only a minority of n=17/36 (47%) glioblastoma and n=2/8 (25%) IDH-mutant astrocytoma patients benefited from targeted therapies, n=7/8 (88%) meningioma, n=9/10 (90%) brain metastases, and n=5/8 (63%) other tumor patients achieved a Neuro-MCBS of 1 or 2, i.e. derived clinical benefit from the molecularly based therapy.
CONCLUSIONS
The Neuro-MCBS is a comprehensive and clinically relevant assessment tool that incorporates clinical, imaging, and survival outcome data to determine the degree of clinical benefit from targeted therapies in patients with primary and secondary CNS tumors. Its incorporation into clinical practice provides an objective outcome measure of clinical utility vs. futility of targeted therapies.
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