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- editorial (2)
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- Institut für diagnostische und interventionelle Neuroradiologie (ehem. Abteilung für Neuroradiologie) (23) (remove)
Background
It is unknown whether technological advancement of stent-retriever devices influences typical observational indicators of safety or effectiveness.
Methods
Observational retrospective study of APERIO® (AP) vs. new generation APERIO® Hybrid (APH) (Acandis®, Pforzheim, Germany) stent-retriever device (01/2019–09/2020) for mechanical thrombectomy (MT) in large vessel occlusion (LVO) stroke. Primary effectiveness endpoint was successful recanalization eTICI (expanded Thrombolysis In Cerebral Ischemia) ≥ 2b67, primary safety endpoint was occurrence of hemorrhagic complications after MT. Secondary outcome measures were time from groin puncture to first pass and successful reperfusion, and the total number of passes needed to achieve the final recanalization result.
Results
A total of 298 patients with LVO stroke who were treated by MT matched the inclusion criteria: 148 patients (49.7%) treated with AP vs. 150 patients (50.3%) treated with new generation APH. Successful recanalization was not statistically different between both groups: 75.7% for AP vs. 79.3% for APH; p = 0.450. Postinterventional hemorrhagic complications and particularly subarachnoid hemorrhage as the entity possibly associated with stent-retriever device type was significantly less frequent in the group treated with the APH: 29.7% for AP and 16.0% for APH; p = 0.005; however, rates of symptomatic hemorrhage with clinical deterioration and in domo mortality were not statistically different. Neither the median number of stent-retriever passages needed to achieve final recanalization, time from groin puncture to first pass, time from groin puncture to final recanalization nor the number of cases in which successful recanalization could only be achieved by using a different stent-retriever as bail-out device differed between both groups.
Conclusion
In the specific example of the APERIO® stent-retriever device, we observed that further technological developments of the new generation device were not associated with disadvantages with respect to typical observational indicators of safety or effectiveness.
Background
Mucopolysaccharidosis type III (Sanfilippo syndrome) is a lysosomal storage disorder, caused by a deficiency in the heparan-N-sulfatase enzyme involved in the catabolism of the glycosaminoglycan heparan sulfate. It is characterized by early nonspecific neuropsychiatric symptoms, followed by progressive neurocognitive impairment in combination with only mild somatic features. In this patient group with a broad clinical spectrum a significant genotype-phenotype correlation with some mutations leading to a slower progressive, attenuated course has been demonstrated.
Case presentation
Our patient had complications in the neonatal period and was diagnosed with Mucopolysaccharidosis IIIa only at the age of 28 years. He was compound heterozygous for the variants p.R245H and p.S298P, the latter having been shown to lead to a significantly milder phenotype.
Conclusions
The diagnostic delay is even more prolonged in this patient population with comorbidities and a slowly progressive course of the disease.
Objectives
Vessel wall enhancement (VWE) may be commonly seen on MRI images of asymptomatic subjects. This study aimed to characterize the VWE of the proximal internal carotid (ICA) and vertebral arteries (VA) in a non-vasculitic elderly patient cohort.
Methods
Cranial MRI scans at 3 Tesla were performed in 43 patients (aged ≥ 50 years) with known malignancy for exclusion of cerebral metastases. For vessel wall imaging (VWI), a high-resolution compressed-sensing black-blood 3D T1-weighted fast (turbo) spin echo sequence (T1 CS-SPACE prototype) was applied post gadolinium with an isotropic resolution of 0.55 mm. Bilateral proximal intradural ICA and VA segments were evaluated for presence, morphology, and longitudinal extension of VWE.
Results
Concentric VWE of the proximal intradural ICA was found in 13 (30%) patients, and of the proximal intradural VA in 39 (91%) patients. Mean longitudinal extension of VWE after dural entry was 13 mm in the VA and 2 mm in the ICA. In 14 of 39 patients (36%) with proximal intradural VWE, morphology of VWE was suggestive of the mere presence of vasa vasorum. In 25 patients (64 %), morphology indicated atherosclerotic lesions in addition to vasa vasorum.
Conclusions
Vasa vasorum may account for concentric VWE within the proximal 2 mm of the ICA and 13 mm of the VA after dural entry in elderly subjects. Concentric VWE in these locations should not be confused with large artery vasculitis. Distal to these segments, VWE may be more likely related to pathologic conditions such as vasculitis.
Background
Chronic heart failure (HF) is known to increase the risk of developing Alzheimer’s dementia significantly. Thus, detecting and preventing mild cognitive impairment, which is common in patients with HF, is of great importance. Serum biomarkers are increasingly used in neurological disorders for diagnostics, monitoring, and prognostication of disease course. It remains unclear if neuronal biomarkers may help detect cognitive impairment in this high-risk population. Also, the influence of chronic HF and concomitant renal dysfunction on these biomarkers is not well understood.
Methods
Within the monocentric Cognition.Matters-HF study, we quantified the serum levels of phosphorylated tau protein 181 (pTau) and neurofilament light chain (NfL) of 146 extensively phenotyped chronic heart failure patients (aged 32 to 85 years; 15.1% women) using ultrasensitive bead-based single-molecule immunoassays. The clinical work-up included advanced cognitive testing and cerebral magnetic resonance imaging (MRI).
Results
Serum concentrations of NfL ranged from 5.4 to 215.0 pg/ml (median 26.4 pg/ml) and of pTau from 0.51 to 9.22 pg/ml (median 1.57 pg/ml). We detected mild cognitive impairment (i.e., T-score < 40 in at least one cognitive domain) in 60% of heart failure patients. pTau (p = 0.014), but not NfL, was elevated in this group. Both NfL (ρ = − 0.21; p = 0.013) and pTau (ρ = − 0.25; p = 0.002) related to the cognitive domain visual/verbal memory, as well as white matter hyperintensity volume and cerebral and hippocampal atrophy. In multivariable analysis, both biomarkers were independently influenced by age (T = 4.6 for pTau; T = 5.9 for NfL) and glomerular filtration rate (T = − 2.4 for pTau; T = − 3.4 for NfL). Markers of chronic heart failure, left atrial volume index (T = 4.6) and NT-proBNP (T = 2.8), were further cardiological determinants of pTau and NfL, respectively. In addition, pTau was also strongly affected by serum creatine kinase levels (T = 6.5) and ferritin (T = − 3.1).
Conclusions
pTau and NfL serum levels are strongly influenced by age-dependent renal and cardiac dysfunction. These findings point towards the need for longitudinal examinations and consideration of frequent comorbidities when using neuronal serum biomarkers.
Mit dieser Studie konnten wir durch retrospektive Beobachtungen zeigen, dass die strahlentherapeutische Behandlung von LGG im Verlauf relativ häufig zum Phänomen der PsPD führt (45,2 %). Darüber hinaus konnten wir in dieser Studie auch nachweisen, dass eine PsPD unabhängig von den drei Arten der analysierten Bestrahlungsmodalitäten aufgetreten ist (p=0,909). Die hohe Inzidenz (45,2 %) der PsPD in dieser und den zitierten Studien unterstreicht die Wichtigkeit der Unterscheidung eines echten PD von einem PsPD. Wir wollen mit dieser Studie dazu beitragen, dass zum einen unnötige Therapiewechsel oder Intensivierungstherapien bei einer PsPD vermieden werden, zum anderen, dass höhere Sicherheit bezüglich der Diagnose eines echten PD erreicht werden kann. Wenn klinisch tätige Ärzte darüber informiert werden, in welchen Lokalisationen bzw. unter welcher Strahlentherapieform ein erhöhtes Risiko für eine PsPD besteht, so können sie ein postradiogenes Wachstum mithilfe der kurzfristig ansteigenden PsPD-spezifischen Parameter im MRT eher einer PsPD als einem PD zuordnen. Auch die klinische Symptomatik muss im Verlauf bei Patienten mit LGG exakt analysiert werden. Die Follow-up Untersuchungen der asymptomatischen Patienten sind ein wichtiger Vergleichsparameter. Die aus dieser Studie gewonnenen Informationen können bei der Beurteilung hinsichtlich des Tumorprogress bei Patienten mit LGG und konsekutiver Radiotherapie helfen und möglicherweise auch Einfluss auf das Design künftiger pädiatrischer LGG Studien nehmen. Inwieweit andere Untersuchungsmodalitäten wie das FET-PET-CT eine exaktere Differenzierung zwischen PsPD und PD ermöglicht, müssen weitere Untersuchungen zeigen. Das FET-PET-CT scheint v.a. eine gute Ergänzung zu der reinen morphologischen Analyse darzustellen, da diese Methode auch die biologische Aktivität des Tumors erfassen kann. Während man mithilfe der MRT-Untersuchungen aufgrund dieser und vorherigen Studien mutmaßen kann, dass es sich bei kurzfristiger Zunahme der drei leitenden Parameter um eine PsPD handeln wird, könnte das FET-PET-CT eine noch größere Sicherheit hinsichtlich der Differenzierung PD versus PsPD geben, wobei einschränkend festzustellen ist, dass die diagnostischen Studien zur FET-PET rar sind.
This proof of concept describes the use of evoked electromyographic (EMG) activation of the facial nerve for intraoperative monitoring of the electrode insertion during cochlear implantation (CI). Intraoperative EMG measurements from the facial nerve were conducted in nine patients undergoing CI implantation. Electric current pulses were emitted from contacts on the CI array during and immediately after electrode insertion. For control, the results of EMG measurements were compared to postoperative flat panel volume computed tomography scans with secondary reconstruction (fpVCT\(_{SECO}\)). During insertion, the EMG response evoked by the electrical stimulation from the CI was growing with the stimulating contact approaching the facial nerve and declined with increasing distance. After full insertion, contacts on the apical half of the CI array stimulated higher EMG responses compared with those on the basal half. Comparison with postoperative imaging demonstrated that electrode contacts stimulating high EMG responses had the shortest distances to the facial nerve. It could be demonstrated that electrically evoked EMG activation of the facial nerve can be used to monitor the progress during CI electrode insertion and to control the intracochlear electrode position after full insertion.
CNS imaging characteristics in fibromyalgia patients with and without peripheral nerve involvement
(2022)
We tested the hypothesis that reduced skin innervation in fibromyalgia syndrome is associated with specific CNS changes. This prospective case–control study included 43 women diagnosed with fibromyalgia syndrome and 40 healthy controls. We further compared the fibromyalgia subgroups with reduced (n = 21) and normal (n = 22) skin innervation. Brains were analysed for cortical volume, for white matter integrity, and for functional connectivity. Compared to controls, cortical thickness was decreased in regions of the frontal, temporal and parietal cortex in the fibromyalgia group as a whole, and decreased in the bilateral pericalcarine cortices in the fibromyalgia subgroup with reduced skin innervation. Diffusion tensor imaging revealed a significant increase in fractional anisotropy in the corona radiata, the corpus callosum, cingulum and fornix in patients with fibromyalgia compared to healthy controls and decreased FA in parts of the internal capsule and thalamic radiation in the subgroup with reduced skin innervation. Using resting-state fMRI, the fibromyalgia group as a whole showed functional hypoconnectivity between the right midfrontal gyrus and the posterior cerebellum and the right crus cerebellum, respectively. The subgroup with reduced skin innervation showed hyperconnectivity between the inferior frontal gyrus, the angular gyrus and the posterior parietal gyrus. Our results suggest that the subgroup of fibromyalgia patients with pronounced pathology in the peripheral nervous system shows alterations in morphology, structural and functional connectivity also at the level of the encephalon. We propose considering these subgroups when conducting clinical trials.
Experimental evidence has emerged that local platelet activation contributes to inflammation and infarct formation in acute ischemic stroke (AIS) which awaits confirmation in human studies. We conducted a prospective observational study on 258 consecutive patients undergoing mechanical thrombectomy (MT) due to large-vessel-occlusion stroke of the anterior circulation (08/2018-05/2020). Intraprocedural microcatheter aspiration of 1 ml of local (occlusion condition) and systemic arterial blood samples (self-control) was performed according to a prespecified protocol. The samples were analyzed for differential leukocyte counts, platelet counts, and plasma levels of the platelet-derived neutrophil-activating chemokine C-X-C-motif ligand (CXCL) 4 (PF-4), the neutrophil attractant CXCL7 (NAP-2), and myeloperoxidase (MPO). The clinical-biological relevance of these variables was corroborated by specific associations with molecular-cellular, structural-radiological, hemodynamic, and clinical-functional parameters. Seventy consecutive patients fulfilling all predefined criteria entered analysis. Mean local CXCL4 (+ 39%: 571 vs 410 ng/ml, P = .0095) and CXCL7 (+ 9%: 693 vs 636 ng/ml, P = .013) concentrations were higher compared with self-controls. Local platelet counts were lower (- 10%: 347,582 vs 383,284/µl, P = .0052), whereas neutrophil counts were elevated (+ 10%: 6022 vs 5485/µl, P = 0.0027). Correlation analyses revealed associations between local platelet and neutrophil counts (r = 0.27, P = .034), and between CXCL7 and MPO (r = 0.24, P = .048). Local CXCL4 was associated with the angiographic degree of reperfusion following recanalization (r = - 0.2523, P = .0479). Functional outcome at discharge correlated with local MPO concentrations (r = 0.3832, P = .0014) and platelet counts (r = 0.288, P = .0181). This study provides human evidence of cerebral platelet activation and platelet-neutrophil interactions during AIS and points to the relevance of per-ischemic thrombo-inflammatory mechanisms to impaired reperfusion and worse functional outcome following recanalization.
Improved radiological examinations with newly developed 3D models may increase understanding of Meniere's disease (MD). The morphology and course of the vestibular aqueduct (VA) in the temporal bone might be related to the severity of MD. The presented study explored, if the VA of MD and non-MD patients can be grouped relative to its angle to the semicircular canals (SCC) and length using a 3D model. Scans of temporal bone specimens (TBS) were performed using micro-CT and micro flat panel volume computed tomography (mfpVCT). Furthermore, scans were carried out in patients and TBS by computed tomography (CT). The angle between the VA and the three SCC, as well as the length of the VA were measured. From these data, a 3D model was constructed to develop the vestibular aqueduct score (VAS). Using different imaging modalities it was demonstrated that angle measurements of the VA are reliable and can be effectively used for detailed diagnostic investigation. To test the clinical relevance, the VAS was applied on MD and on non-MD patients. Length and angle values from MD patients differed from non-MD patients. In MD patients, significantly higher numbers of VAs could be assigned to a distinct group of the VAS. In addition, it was tested, whether the outcome of a treatment option for MD can be correlated to the VAS.
Purpose
For further improvements in cochlear implantation, the measurement of the cochlear duct length (CDL) and the determination of the electrode contact position (ECP) are increasingly in the focus of clinical research. Usually, these items were investigated by multislice computed tomography (MSCT). The determination of ECP was only possible by research programs so far. Flat-panel volume computed tomography (fpVCT) and its secondary reconstructions (fpVCT\(_{SECO}\)) allow for high spatial resolution for the visualization of the temporal bone structures. Using a newly developed surgical planning software that enables the evaluation of CDL and the determination of postoperative ECP, this study aimed to investigate the combination of fpVCT and otological planning software to improve the implementation of an anatomically based cochlear implantation.
Methods
Cochlear measurements were performed utilizing surgical planning software in imaging data (MSCT, fpVCT and fpVCT\(_{SECO}\)) of patients with and without implanted electrodes.
Results
Measurement of the CDL by the use of an otological planning software was highly reliable using fpVCT\(_{SECO}\) with a lower variance between the respective measurements compared to MSCT. The determination of the inter-electrode-distance (IED) between the ECP was improved in fpVCT\(_{SECO}\) compared to MSCT.
Conclusion
The combination of fpVCT\(_{SECO}\) and otological planning software permits a simplified and more reliable analysis of the cochlea in the pre- and postoperative setting. The combination of both systems will enable further progress in the development of an anatomically based cochlear implantation.
Purpose
Patients suffering from aggressive systemic peripheral lymphoma with primary central nervous system involvement (PCL) are a rare and sparsely investigated population. Recommended treatment regimens include a combination of intrathecal and systemic chemotherapy as well as whole brain radiotherapy while offering relatively poor survival.
Methods
We conducted a single-center retrospective study that analyzed safety and outcome of 4 + 4 cycles Rituximab (R)-CHOP and R-high-dose Methotrexate (HD-MTX) for newly diagnosed, transplant-eligible patients ("Ping-Pong"), followed by Cytarabine (AraC)/Thiotepa (TT), BCNU/TT, and autologous hematologic stem cell transplantation (aHSCT). We retrospectively analyzed a set of 16 patients with high-intermediate or high-risk IPI status.
Results
Overall response rate to Ping-Pong was 100% measured by CT/MRI, including 93.75% complete remissions after BCNU/TT followed by PBSCT. One patient failed to qualify for high-dose chemotherapy due to progression when receiving Cytarabine/TT. All patients experienced grade III adverse events, 3 of them a grade IV adverse event. Estimated progression-free survival is 93.75% after a 4.8-year follow-up currently.
Conclusion
Our study suggests high effectivity of R-CHOP with mid-cycle MTX with aHSCT consolidation towards acceptable OS results in this challenging patient population.
Background
Anderson–Fabry disease (FD) is an X-linked lysosomal storage disorder with varying organ involvement and symptoms, depending on the underlying mutation in the alpha-galactosidase A gene (HGNC: GLA). With genetic testing becoming more readily available, it is crucial to precisely evaluate pathogenicity of each genetic variant, in order to determine whether there is or might be not a need for FD-specific therapy in affected patients and relatives at the time point of presentation or in the future.
Methods
This case series investigates the clinical impact of the specific GLA gene variant c.376A>G (p.Ser126Gly) in five (one heterozygous and one homozygous female, three males) individuals from different families, who visited our center between 2009 and 2021. Comprehensive neurological, nephrological and cardiac examinations were performed in all cases. One patient received a follow-up examination after 12 years.
Results
Index events leading to suspicion of FD were mainly unspecific neurological symptoms. However, FD-specific biomarkers, imaging examinations (i.e., brain MRI, heart MRI), and tissue-specific diagnostics, including kidney and skin biopsies, did not reveal evidence for FD-specific symptoms or organ involvement but showed normal results in all cases. This includes findings from 12-year follow-up in one patient with renal biopsy.
Conclusion
These findings suggest that p.Ser126Gly represents a benign GLA gene variant which per se does not cause FD. Precise clinical evaluation in individuals diagnosed with genetic variations of unknown significance should be performed to distinguish common symptoms broadly prevalent in the general population from those secondary to FD.
Merkel cell carcinoma is a rare, highly aggressive skin cancer with neuroendocrine differentiation. Immune checkpoint inhibition has significantly improved treatment outcomes in metastatic disease with response rates to programmed cell death protein 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) inhibition of up to 62%. However, primary and secondary resistance to PD-1/PD-L1 inhibition remains a so far unsolved clinical challenge since effective and safe treatment options for these patients are lacking.Fourteen patients with advanced (non-resectable stage III or stage IV, Union international contre le cancer 2017) Merkel cell carcinoma with primary resistance to the PD-L1 inhibitor avelumab receiving subsequent therapy (second or later line) with ipilimumab plus nivolumab (IPI/NIVO) were identified in the prospective multicenter skin cancer registry ADOREG. Five of these 14 patients were reported previously and were included in this analysis with additional follow-up. Overall response rate, progression-free survival (PFS), overall survival (OS) and adverse events were analyzed.All 14 patients received avelumab as first-line treatment. Thereof, 12 patients had shown primary resistance with progressive disease in the first tumor assessment, while two patients had initially experienced a short-lived stabilization (stable disease). Six patients had at least one systemic treatment in between avelumab and IPI/NIVO. In total, 7 patients responded to IPI/NIVO (overall response rate 50%), and response was ongoing in 4 responders at last follow-up. After a median follow-up of 18.85 months, median PFS was 5.07 months (95% CI 2.43—not available (NA)), and median OS was not reached. PFS rates at 12 months and 24 months were 42.9% and 26.8 %, respectively. The OS rate at 36 months was 64.3%. Only 3 (21%) patients did not receive all 4 cycles of IPI/NIVO due to immune-related adverse events.In this multicenter evaluation, we observed high response rates, a durable benefit and promising OS rates after treatment with later-line combined IPI/NIVO. In conclusion, our patient cohort supports our prior findings with an encouraging activity of second-line or later-line IPI/NIVO in patients with anti-PD-L1-refractory Merkel cell carcinoma.
Magnetic nanoparticles (MNPs) have been adapted for many applications, e.g., bioassays for the detection of biomarkers such as antibodies, by controlled engineering of specific surface properties. Specific measurement of such binding states is of high interest but currently limited to highly sensitive techniques such as ELISA or flow cytometry, which are relatively inflexible, difficult to handle, expensive and time-consuming. Here we report a method named COMPASS (Critical-Offset-Magnetic-Particle-SpectroScopy), which is based on a critical offset magnetic field, enabling sensitive detection to minimal changes in mobility of MNP ensembles, e.g., resulting from SARS-CoV-2 antibodies binding to the S antigen on the surface of functionalized MNPs. With a sensitivity of 0.33 fmole/50 µl (≙7 pM) for SARS-CoV-2-S1 antibodies, measured with a low-cost portable COMPASS device, the proposed technique is competitive with respect to sensitivity while providing flexibility, robustness, and a measurement time of seconds per sample. In addition, initial results with blood serum demonstrate high specificity.
Background: During the last decade, cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) was a current research focus without a standardized classification in digital subtraction angiography (DSA). This study was performed to investigate a device-independent visual cerebral vasospasm classification for endovascular treatment. Methods: The analyses are DSA based rather than multimodal. Ten defined points of intracranial arteries were measured in 45 patients suffering from cerebral vasospasm after SAH at three time points (hospitalization, before spasmolysis, control after six months). Mathematical clustering of vessel diameters was performed to generate four objective grades for comparison. Six interventional neuroradiologists in two groups scored 237 DSAs after a new visual classification (grade 0–3) developed on a segmental pattern of vessel contraction. For the second group, a threshold-based criterion was amended. Results: The raters had a reproducibility of 68.4% in the first group and 75.2% in the second group. The complementary threshold-based criterion increased the reproducibility by about 6.8%, while the rating deviated more from the mathematical clustering in all grades. Conclusions: The proposed visual classification scheme of cerebral vasospasm is suitable as a standard grading procedure for endovascular treatment. There is no advantage of a threshold-based criterion that compensates for the effort involved. Automated vessel analysis is superior to compare inter-group results in research settings.
Recurrent medulloblastomas are associated with survival rates <10%. Adequate multimodal therapy is being discussed as having a major impact on survival. In this study, 93 patients with recurrent medulloblastoma treated in the German P-HIT-REZ 2005 Study were analyzed for survival (PFS, OS) dependent on patient, disease, and treatment characteristics. The median age at the first recurrence was 10.1 years (IQR: 6.9–16.1). Median PFS and OS, at first recurrence, were 7.9 months (CI: 5.7–10.0) and 18.5 months (CI: 13.6–23.5), respectively. Early relapses/progressions (<18 months, n = 30/93) found mainly in molecular subgroup 3 were associated with markedly worse median PFS (HR: 2.34) and OS (HR: 3.26) in regression analyses. A significant survival advantage was found for the use of volume-reducing surgery as well as radiotherapy. Intravenous chemotherapy with carboplatin and etoposide (ivCHT, n = 28/93) showed improved PFS and OS data and the best objective response rate (ORR) was 66.7% compared to oral temozolomide (oCHT, n = 47/93) which was 34.8%. Intraventricular (n = 43) as well as high-dose chemotherapy (n = 17) at first relapse was not related to a significant survival benefit. Although the results are limited due to a non-randomized study design, they may serve as a basis for future treatment decisions in order to improve the patients' survival.
Aims
Cognitive dysfunction occurs frequently in patients with heart failure (HF), but early detection remains challenging. Serum glial fibrillary acidic protein (GFAP) is an emerging biomarker of cognitive decline in disorders of primary neurodegeneration such as Alzheimer's disease. We evaluated the utility of serum GFAP as a biomarker for cognitive dysfunction and structural brain damage in patients with stable chronic HF.
Methods and results
Using bead-based single molecule immunoassays, we quantified serum levels of GFAP in patients with HF participating in the prospective Cognition.Matters-HF study. Participants were extensively phenotyped, including cognitive testing of five separate domains and magnetic resonance imaging (MRI) of the brain. Univariable and multivariable models, also accounting for multiple testing, were run. One hundred and forty-six chronic HF patients with a mean age of 63.8 ± 10.8 years were included (15.1% women). Serum GFAP levels (median 246 pg/mL, quartiles 165, 384 pg/mL; range 66 to 1512 pg/mL) did not differ between sexes. In the multivariable adjusted model, independent predictors of GFAP levels were age (T = 5.5; P < 0.001), smoking (T = 3.2; P = 0.002), estimated glomerular filtration rate (T = −4.7; P < 0.001), alanine aminotransferase (T = −2.1; P = 0.036), and the left atrial end-systolic volume index (T = 3.4; P = 0.004). NT-proBNP but not serum GFAP explained global cerebral atrophy beyond ageing. However, serum GFAP levels were associated with the cognitive domain visual/verbal memory (T = −3.0; P = 0.003) along with focal hippocampal atrophy (T = 2.3; P = 0.025).
Conclusions
Serum GFAP levels are affected by age, smoking, and surrogates of the severity of HF. The association of GFAP with memory dysfunction suggests that astroglial pathologies, which evade detection by conventional MRI, may contribute to memory loss beyond ageing in patients with chronic HF.
During ischemic stroke, infarct growth before recanalization diminishes functional outcome. Hence, adjunct treatment options to protect the ischemic penumbra before recanalization are eagerly awaited. In experimental stroke targeting two different pathways conferred protection from penumbral tissue loss: (1) enhancement of hypoxic tolerance of neurons by deletion of the calcium channel subunit Orai2 and (2) blocking of detrimental lymphocyte–platelet responses. However, until now, no preclinical stroke study has assessed the potential of combining neuroprotective with anti-thrombo-inflammatory interventions to augment therapeutic effects. We induced focal cerebral ischemia in Orai2-deficient (Orai2\(^{-/-}\)) mice by middle cerebral artery occlusion (MCAO). Animals were treated with anti-glycoprotein Ib alpha (GPIbα) Fab fragments (p0p/B Fab) blocking GPIbα–von Willebrand factor (vWF) interactions. Rat immunoglobulin G (IgG) Fab was used as the control treatment. The extent of infarct growth before recanalization was assessed at 4 h after MCAO. Moreover, infarct volumes were determined 6 h after recanalization (occlusion time: 4 h). Orai2 deficiency significantly halted cerebral infarct progression under occlusion. Inhibition of platelet GPIbα further reduced primary infarct growth in Orai2\(^{-/-}\) mice. During ischemia–reperfusion, upon recanalization, mice were likewise protected. All in all, we show that neuroprotection in Orai2\(^{-/-}\) mice can be augmented by targeting thrombo-inflammation. This supports the clinical development of combined neuroprotective/anti-platelet strategies in hyper-acute stroke.
Purpose
Surgery is a standard therapy for tympanojugular paragangliomas (TJP). Maintaining the quality of life (QoL) requires functional preservation. The flexible CO\(_2\) laser allows contact-free tumor removal. This retrospective study compares the postoperative functional outcomes of TJP surgery with and without the flexible CO\(_2\) laser.
Methods
Between 2005 and 2019, 51 patients with TJP were surgically treated at a tertiary hospital. Until 2012, 17 patients received conventional surgery. Thereafter, the flexible laser was used in 34 patients. Tumor extend, pre- and postoperative cranial nerve function, and complications were compared between the groups.
Results
The cohort consisted of 33 class A and B tumors and 18 class C and D tumors. Preoperative embolization was performed in 17 cases. Class C/D TJP were usually removed via an infratemporal fossa type A approach. Gross total tumor removal was achieved in 14/18 class C/D tumors. 3/51 patients suffered from long-term partial or complete facial palsy. No differences in post-therapeutic cranial nerve function or complications were noted between the conventional and laser group. One recurrence was observed after complete tumor resection.
Conclusion
The flexible CO\(_2\) laser was shown to be a safe and effective alternative to conventional bipolar cauterization, which is appreciated by the surgeon in these highly vascularized tumors. Both techniques allowed a high tumor control rate and good long-term results also from a functional point of view.
As radiotherapy is an important part of the treatment in a variety of pediatric tumors of the central nervous system (CNS), proton beam therapy (PBT) plays an evolving role due to its potential benefits attributable to the unique dose distribution, with the possibility to deliver high doses to the target volume while sparing surrounding tissue. Children receiving PBT for an intracranial tumor between August 2013 and October 2017 were enrolled in the prospective registry study KiProReg. Patient’s clinical data including treatment, outcome, and follow-up were analyzed using descriptive statistics, Kaplan–Meier, and Cox regression analysis. Adverse events were scored according to the Common Terminology Criteria for Adverse Events (CTCAE) 4.0 before, during, and after PBT. Written reports of follow-up imaging were screened for newly emerged evidence of imaging changes, according to a list of predefined keywords for the first 14 months after PBT. Two hundred and ninety-four patients were enrolled in this study. The 3-year overall survival of the whole cohort was 82.7%, 3-year progression-free survival was 67.3%, and 3-year local control was 79.5%. Seventeen patients developed grade 3 adverse events of the CNS during long-term follow-up (new adverse event n = 7; deterioration n = 10). Two patients developed vision loss (CTCAE 4°). This analysis demonstrates good general outcomes after PBT.
It’s time to go …
(2022)