Tumor size, treatment patterns, and survival in neuro-oncology patients before and during the COVID-19 pandemic.

The COVID-19 pandemic has disrupted healthcare delivery worldwide, leading to significant delays in cancer diagnosis and treatment. This study aimed to investigate the impact of the pandemic on the diagnosis and treatment of malignant brain tumors, specifically glioblastoma (GBM) and cerebral metastasis (CM), in a specialized neuro-oncology center. We analyzed data from 236 patients diagnosed with previously unknown malignant brain tumors between January 2018 and December 2021. Patients were classified into two groups: pre-COVID (January 2018 to December 2019) and COVID (January 2020 to December 2021). Tumor volumes were compared between the two groups and factors affecting tumor volumes were studied. Of 236 patients diagnosed with previously unknown malignant brain tumors, 114 were in the pre-COVID group and 122 were in the COVID group. Median tumor volumes at first diagnosis were significantly larger in the COVID group compared to the pre-COVID group (21.7 vs 15.7 cm3; p < 0.05). The survival times for the overall cohort and the GBM and CM subgroups did not differ significantly between the pre-COVID and COVID periods. Delays in diagnosis and treatment during the COVID-19 pandemic led to larger tumor volumes at diagnosis for patients with malignant brain tumors. However, these larger tumors did not result in worse survival outcomes. This counterintuitive finding highlights the crucial role of specialized neuro-oncological centers in mitigating the potential negative impact of delayed treatment and emphasizes the need for continued access to specialized care during times of crisis.

Invasive Diagnostic and Therapeutic Management of Cerebral VasoSpasm after Aneurysmal Subarachnoid Hemorrhage (IMCVS)-A Phase 2 Randomized Controlled Trial.

Cerebral vasospasm (CVS) is associated with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH). The most frequently used form of rescue therapy for CVS is invasive endovascular therapy. Due to a lack of prospective data, we performed a prospective randomized multicenter trial (NCT01400360). A total of 34 patients in three centers were randomized to invasive endovascular treatment or conservative therapy at diagnosis of relevant CVS onset. Imaging data was assessed by a neuroradiologist blinded for treatment allocation. Primary outcome measure was development of DCI. Secondary endpoints included clinical outcome at 6 months after SAH. A total of 18 of the 34 patients were treated conservatively, and 16 patients were treated with invasive endovascular treatment for CVS. There was no statistical difference in the rate of cerebral infarctions either at initial or at the follow-up MRI between the groups. However, the outcome at 6 months was better in patients treated conservatively (mRs 2 ± 1.5 vs. 4 ± 1.8, p = 0.005). Invasive endovascular treatment for CVS does not lead to a lower rate of DCI but might lead to poorer outcomes compared to induced hypertension. The potential benefits of endovascular treatment for CVS need to be addressed in further studies, searching for a subgroup of patients who may benefit.

Cortical and subcortical grey matter atrophy in Amyotrophic Lateral Sclerosis correlates with measures of disease accumulation independent of disease aggressiveness.

There is a growing demand for reliable biomarkers to monitor disease progression in Amyotrophic Lateral Sclerosis (ALS) that also take the heterogeneity of ALS into account. In this study, we explored the association between Magnetic Resonance Imaging (MRI)-derived measures of cortical thickness (CT) and subcortical grey matter (GM) volume with D50 model parameters. T1-weighted MRI images of 72 Healthy Controls (HC) and 100 patients with ALS were analyzed using Surface-based Morphometry for cortical structures and Voxel-based Morphometry for subcortical Region-Of-Interest analyses using the Computational Anatomy Toolbox (CAT12). In Inter-group contrasts, these parameters were compared between patients and HC. Further, the D50 model was used to conduct subgroup-analyses, dividing patients by a) Phase of disease covered at the time of MRI-scan and b) individual overall disease aggressiveness. Finally, correlations between GM and D50 model-derived parameters were examined. Inter-group analyses revealed ALS-related cortical thinning compared to HC located mainly in frontotemporal regions and a decrease in GM volume in the left hippocampus and amygdala. A comparison of patients in different phases showed further cortical and subcortical GM atrophy along with disease progression. Correspondingly, regression analyses identified negative correlations between cortical thickness and individual disease covered. However, there were no differences in CT and subcortical GM between patients with low and high disease aggressiveness. By application of the D50 model, we identified correlations between cortical and subcortical GM atrophy and ALS-related functional disability, but not with disease aggressiveness. This qualifies CT and subcortical GM volume as biomarkers representing individual disease covered to monitor therapeutic interventions in ALS.

Human Borna disease virus 1 (BoDV-1) encephalitis cases in the north and east of Germany.

In 2021, three encephalitis cases due to the Borna disease virus 1 (BoDV-1) were diagnosed in the north and east of Germany. The patients were from the states of Thuringia, Saxony-Anhalt, and Lower Saxony. All were residents of known endemic areas for animal Borna disease but without prior diagnosed human cases. Except for one recently detected case in the state of Brandenburg, all >30 notified cases had occurred in, or were linked to, the southern state of Bavaria. Of the three detected cases described here, two infections were acute, while one infection was diagnosed retrospectively from archived brain autopsy tissue samples. One of the acute cases survived, but is permanently disabled. The cases were diagnosed by various techniques (serology, molecular assays, and immunohistology) following a validated testing scheme and adhering to a proposed case definition. Two cases were classified as confirmed BoDV-1 encephalitis, while one case was a probable infection with positive serology and typical brain magnetic resonance imaging, but without molecular confirmation. Of the three cases, one full virus genome sequence could be recovered. Our report highlights the need for awareness of a BoDV-1 etiology in cryptic encephalitis cases in all areas with known animal Borna disease endemicity in Europe, including virus-endemic regions in Austria, Liechtenstein, and Switzerland. BoDV-1 should be actively tested for in acute encephalitis cases with residence or rural exposure history in known Borna disease-endemic areas.

Complicated Long Term Vaccine Induced Thrombotic Immune Thrombocytopenia-A Case Report.

BACKGROUND AND OBJECTIVES: Vaccine induced thrombotic thrombocytopenia (VITT) may occur after COVID-19 vaccination with recombinant adenoviral vector-based vaccines. VITT can present as cerebral sinus and venous thrombosis (CSVT), often complicated by intracranial hemorrhage. Today it is unclear, how long symptomatic VITT can persist. Here, we report the complicated long-term course of a VITT patient with extremely high titers of pathogenic anti-platelet factor 4 (PF4)-IgG antibodies. METHODS: Clinical and laboratory findings are presented, including the course of platelet counts, D-Dimer levels, clinical presentation, imaging, SARS-CoV-2-serological and immunological, platelet activating anti-PF4-IgG, as well as autopsy findings. RESULTS: The patient presented with extended superior sagittal sinus thrombosis with accompanying bifrontal intracerebral hemorrhage. Repeated treatment with intravenous immune globuline (IVIG) resolved recurrent episodes of thrombocytopenia. Moreover, the patient's serum remained strongly positive for platelet-activating anti-PF4-IgG over three months. After a period of clinical stabilization, the patient suffered a recurrent and fatal intracranial hemorrhage. CONCLUSIONS: Complicated VITT with extremely high anti-PF4-IgG titers over three months can induce recurrent thrombocytopenia despite treatment with IVIG and anticoagulation. Plasma exchange, immunoadsorption, and /or immunosuppressive treatment may be considered in complicated VITT to reduce extraordinarily high levels of anti-PF4-IgG. Long-term therapy in such cases must take the individual bleeding risk and CSVT risk into account.

Feasibility of the Big 5-Jena eCS Protocol : First Experience Implementing a New Extended CT Protocol in the Initial Diagnostics of Ischemic Stroke.

PURPOSE: The most common protocols in the initial diagnostic of acute ischemic stroke do not assess cardiogenic or aortic causes of embolism. These are usually evaluated later by transthoracic (TTE) or transesophageal (TEE) echocardiography. This study aimed to evaluate the feasibility of a diagnostic tool for thoracic cardiovascular thrombi according to the first experience with a new extended cardio-stroke protocol (Big 5-Jena eCS protocol) in acute stroke patients. METHODS: Retrospective analyses of the tomography scans database of the Jena University Hospital were performed. We included a total of 67 patients in the feasibility analyses, based on the evaluation of three outcomes. RESULTS: Primary outcome: the Big 5-Jena eCS protocol was able to detect thoracic cardiovascular thrombi in a total of 20 patients in different locations including the arch of the aorta, the aortic valve, the left atrium, the left atrial appendage, the left ventricle, and the pulmonary arteries. Secondary outcome: implementating the protocol did not result in a significant elevation of the radiation exposure compared to traditional protocols. Tertiary outcome: the new protocol identified seven cases that were considered negative by echocardiography. CONCLUSION: The implementation of an extended cardio-stroke protocol is feasible, no significantly time-consuming, acquiring assessable imaging, and maintaining radiation exposure acceptable. The Big 5-Jena eCS protocol was also able to detect some thrombi not reported by TTE or TEE; however, due to our data's explorative character, a conclusive comparison with cardiac ultrasound is not possible. A prospective pilot study and clinical trials should be conducted to assess the diagnostic accuracy of this protocol compared to echocardiography and determine the potential impact on diagnostic and treatment decisions.

Patterns of grey and white matter changes differ between bulbar and limb onset amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that is characterized by a high heterogeneity in patients' disease course. Patients with bulbar onset of symptoms (b-ALS) have a poorer prognosis than patients with limb onset (l-ALS). However, neuroimaging correlates of the assumed biological difference between b-ALS and l-ALS may have been obfuscated by patients' diversity in the disease course. We conducted Voxel-Based-Morphometry (VBM) and Tract-Based-Spatial-Statistics (TBSS) in a group of 76 ALS patients without clinically relevant cognitive deficits. The subgroups of 26 b-ALS and 52 l-ALS patients did not differ in terms of disease Phase or disease aggressiveness according to the D50 progression model. VBM analyses showed widespread ALS-related changes in grey and white matter, that were more pronounced for b-ALS. TBSS analyses revealed that b-ALS was predominantly characterized by frontal fractional anisotropy decreases. This demonstrates a higher degree of neurodegenerative burden for the group of b-ALS patients in comparison to l-ALS. Correspondingly, higher bulbar symptom burden was associated with right-temporal and inferior-frontal grey matter density decreases as well as fractional anisotropy decreases in inter-hemispheric and long association tracts. Contrasts between patients in Phase I and Phase II further revealed that b-ALS was characterized by an early cortical pathology and showed a spread only outside primary motor regions to frontal and temporal areas. In contrast, l-ALS showed ongoing structural integrity loss within primary motor-regions until Phase II. We therefore provide a strong rationale to treat both onset types of disease separately in ALS studies.

Disease aggressiveness signatures of amyotrophic lateral sclerosis in white matter tracts revealed by the D50 disease progression model.

Numerous neuroimaging studies in amyotrophic lateral sclerosis (ALS) have reported links between structural changes and clinical data; however phenotypic and disease course heterogeneity have occluded robust associations. The present study used the novel D50 model, which distinguishes between disease accumulation and aggressiveness, to probe correlations with measures of diffusion tensor imaging (DTI). DTI scans of 145 ALS patients and 69 controls were analyzed using tract-based-spatial-statistics of fractional anisotropy (FA), mean- (MD), radial (RD), and axial diffusivity (AD) maps. Intergroup contrasts were calculated between patients and controls, and between ALS subgroups: based on (a) the individual disease covered (Phase I vs. II) or b) patients' disease aggressiveness (D50 value). Regression analyses were used to probe correlations with model-derived parameters. Case-control comparisons revealed widespread ALS-related white matter pathology with decreased FA and increased MD/RD. These affected pathways showed also correlations with the accumulated disease for increased MD/RD, driven by the subgroup of Phase I patients. No significant differences were noted between patients in Phase I and II for any of the contrasts. Patients with high disease aggressiveness (D50 < 30 months) displayed increased AD/MD in bifrontal and biparietal pathways, which was corroborated by significant voxel-wise regressions with D50. Application of the D50 model revealed associations between DTI measures and ALS pathology in Phase I, representing individual disease accumulation early in disease. Patients' overall disease aggressiveness correlated robustly with the extent of DTI changes. We recommend the D50 model for studies developing/validating neuroimaging or other biomarkers for ALS.

Experiences from treating seven adult 5q spinal muscular atrophy patients with Nusinersen.

BACKGROUND: The antisense oligonucleotide Nusinersen recently became the first approved drug against spinal muscular atrophy (SMA). It was approved for all ages, albeit the clinical trials were conducted exclusively on children. Hence, clinical data on adults being treated with Nusinersen is scarce. In this case series, we report on drug application, organizational demands, and preliminary effects during the first 10 months of treatment with Nusinersen in seven adult patients. METHODS: All patients received intrathecal injections with Nusinersen. In cases with severe spinal deformities, we performed computed tomography (CT)-guided applications. We conducted a total of 40 administrations of Nusinersen. We evaluated the patients with motor, pulmonary, and laboratory assessments, and tracked patient-reported outcome. RESULTS: Intrathecal administration of Nusinersen was successful in most patients, even though access to the lumbar intrathecal space in adults with SMA is often challenging. No severe adverse events occurred. Six of the seven patients reported stabilization of motor function or reduction in symptom severity. The changes in the assessed scores did not reach a significant level within this short time period. CONCLUSIONS: Treating adult SMA patients with Nusinersen is feasible and most patients consider it beneficial. It demands a complex organizational and interdisciplinary effort. Due to the slowly decreasing motor functions in adult SMA patients, long observation phases for this recently approved treatment are needed to allow conclusions about effectiveness of Nusinersen in adults.

Applying the D50 disease progression model to gray and white matter pathology in amyotrophic lateral sclerosis.

Therapeutic management and research in Amyotrophic Laterals Sclerosis (ALS) have been limited by the substantial heterogeneity in progression and anatomical spread that are endemic of the disease. Neuroimaging biomarkers represent powerful additions to the current monitoring repertoire but have yielded inconsistent associations with clinical scores like the ALS functional rating scale. The D50 disease progression model was developed to address limitations with clinical indices and the difficulty obtaining longitudinal data in ALS. It yields overall disease aggressiveness as time taken to reach halved functionality (D50); individual disease covered in distinct phases; and calculated functional state and calculated functional loss as acute descriptors of local disease activity. It greatly reduces the noise of the ALS functional rating scale and allows the comparison of highly heterogeneous disease and progression subtypes. In this study, we performed Voxel-Based Morphometry for 85 patients with ALS (60.1 ± 11.5 years, 36 female) and 62 healthy controls. Group-wise comparisons were performed separately for gray matter and white matter using ANCOVA testing with threshold-free cluster enhancement. ALS-related widespread gray and white matter density decreases were observed in the bilateral frontal and temporal lobes (p < 0.001, family-wise error corrected). We observed a progressive spread of structural alterations along the D50-derived phases, that were primarily located in frontal, temporal and occipital gray matter areas, as well as in supratentorial neuronal projections (p < 0.001 family-wise error corrected). ALS patients with higher overall disease aggressiveness (D50 < 30 months) showed a distinct pattern of supratentorial white matter density decreases relative to patients with lower aggressiveness; no significant differences were observed for gray matter density (p < 0.001 family-wise error corrected). The application of the D50 disease progression model separates measures of disease aggressiveness from disease accumulation. It revealed a strong correlation between disease phases and in-vivo measures of cerebral structural integrity. This study underscores the proposed corticofugal spread of cerebral pathology in ALS. We recommend application of the D50 model in studies linking clinical data with neuroimaging correlates.

Acute Stroke Treatment by Surgical Recanalization of Extracranial Internal Carotid Artery Occlusion: A Single Center Experience.

Ischemic stroke due to an acute occlusion of the extracranial internal carotid artery (eICA) is associated with high morbidity and mortality. The best treatment option remains unclear. This study aims to increase the available therapeutic experience documented for surgical recanalization of acute eICA occlusions. We retrospectively reviewed all hospital records of the University Hospital Jena between 2006 and 2018 to identified patients with acute ischemic stroke due to an occlusion of the eICA who underwent emergent surgical recanalization. We analyzed clinical data, surgical reports, imaging data, and outpatient records. The primary outcome parameter was the modified Rankin Scale (mRS) at 3 months. During the survey, 12 patients (mean age: 62.3 ± 10.8 years; range: 35-87) underwent emergent surgical recanalization for an acutely symptomatic eICA occlusion. All patients presented with neurological deficits with a mean National Institutes of Health Stroke Scale score at admission of 15.0 ± 5.1 (range 2-23). Patients were selected for surgery mainly due to the extent of the perfusion mismatch, while stroke severity and age were also considered. The median time from symptom onset to surgery was 309 ± 122 minutes (range 112-650 minutes). Complete recanalization was obtained in all 12 patients. No patient deteriorated postoperatively, no intracranial hemorrhage was observed, and no patient died in the following 3 months. Favorable outcomes (mRS: 0-2) after 3 months were achieved in 7 of 12 patients. The current study adds support to previous findings that the surgical recanalization of acute eICA occlusions is a possible and safe treatment option. However, a critical patient selection based on mismatch size in perfusion imaging is crucially important for successful treatment.

International survey on neuroradiological interventional and therapeutic devices and materials.

A web-based survey was performed among the members of the World Federation of Interventional and Therapeutic Neuroradiology to determine the differences in availability, pricing, and performance of endovascular devices with special focus on coils, intra-arterial stroke devices, detachable balloons, and liquid embolic materials. The results of this survey show that the quality of the majority of interventional neuroradiology devices is good and compatibility issues are limited. Individual action towards suppliers is recommended to discuss the availability and pricing of devices and embolization materials.

Mechanical thrombectomy in basilar artery thrombosis: technical advances and safety in a 10-year experience.

PURPOSE: Multiple endovascular devices have been used for mechanical thrombectomy (MT) in basilar artery occlusion (BAO) for >10 years. Based on a single-center experience during the course of one decade, we present data on safety and efficacy of previous MT devices compared with modern stent retriever and suction thrombectomy. MATERIALS AND METHODS: Eighty-one patients (29 women, 52 men, mean age 61.5 years, range 17-90) with angiographically confirmed BAO that had been treated by MT between 2001 and 2011 were retrospectively evaluated. Patients in group 1 (n = 60) had been treated between 2001 and 2008 with different devices available at that time. Patients in group 2 (n = 21) had been treated by modern stent retriever or local suction devices between 2008 and 2011. Recanalization rate, needle to recanalization time, procedure-related complications, and distal embolization of thrombotic material were recorded and compared. RESULTS: Recanalization rates of 95% were high in both groups. Procedure-related dissection (n = 5) and subarachnoid hemorrhage (n = 9) occurred in group 1 but not in group 2 (p < 0.016). Needle-to-recanalization time was less than half in group 2 compared with group 1 (54.6 vs. 132.3 min, p < 0.01). Frequency of distal embolization was comparable in both groups (47%). CONCLUSION: High recanalization rates have been achieved since the introduction of MT in BAO. However, modern stent retriever and suction devices allow for safer and more rapid recanalization compared with previous MT devices.

Cryptogenic left main thrombosis: successful mechanical clot retrieval with a self-expanding trapping device.

We present the case of a 52-year-old male with ST-segment elevation myocardial infarction due to a spontaneous large left main thrombosis, without any angiographic evidence for coronary artery disease. After multiple unsuccessful attempts of thrombaspiration the large clot was mechanically retrieved by a flow restoration device that was primarily made for intracranial interventions. Intravascular ultrasound revealed marginal lumen narrowing after the intervention, but the final coronary angiogram showed a patent left main and there was no relevant stenosis remaining.

Sex differences in oxytocin receptor binding in forebrain regions: correlations with social interest in brain region- and sex- specific ways.

Social interest reflects the motivation to approach a conspecific for the assessment of social cues and is measured in rats by the amount of time spent investigating conspecifics. Virgin female rats show lower social interest towards unfamiliar juvenile conspecifics than virgin male rats. We hypothesized that the neuropeptide oxytocin (OT) may modulate sex differences in social interest because of the involvement of OT in pro-social behaviors. We determined whether there are sex differences in OT system parameters in the brain and whether these parameters would correlate with social interest. We also determined whether estrus phase or maternal experience would alter low social interest and whether this would correlate with changes in OT system parameters. Our results show that regardless of estrus phase, females have significantly lower OT receptor (OTR) binding densities than males in the majority of forebrain regions analyzed, including the nucleus accumbens, caudate putamen, lateral septum, bed nucleus of the stria terminalis, medial amygdala, and ventromedial hypothalamus. Interestingly, male social interest correlated positively with OTR binding densities in the medial amygdala, while female social interest correlated negatively with OTR binding densities in the central amygdala. Proestrus/estrus females showed similar social interest to non-estrus females despite increased OTR binding densities in several forebrain areas. Maternal experience had no immediate or long-lasting effects on social interest or OT brain parameters except for higher OTR binding in the medial amygdala in primiparous females. Together, these findings demonstrate that there are robust sex differences in OTR binding densities in multiple forebrain regions of rats and that OTR binding densities correlate with social interest in brain region- and sex-specific ways.

Delineation of alar ligament morphology: comparison of magnetic resonance imaging at 1.5 and 3 Tesla.

Rupture of the alar and transverse ligaments due to whiplash injury can lead to upper cervical spine instability and subsequent neurological deterioration. The purpose of this study was to evaluate the normal anatomical variability of the alar ligaments in asymptomatic individuals with 3-T magnetic resonance imaging (MRI) and to compare the findings with standard 1.5-T examinations. Thirty-six participants underwent 3-T and 1.5-T MRIs. Magnetic resonance imaging findings were analyzed by classifying the alar ligaments with regard to the features detectability, signal intensity compared with muscle tissue, homogeneity, shape, spatial orientation, and symmetry. Delineation of the alar ligaments was significantly better on 3-T images, which were subjectively preferred for evaluation. The alar ligaments showed great variability. In the majority of participants, the alar ligaments were hypointense to muscle tissue, inhomogeneous, and different in shape and orientation. A statistically significantly higher number of ligaments appeared symmetric on 3-T imaging, indicating that 1.5-T imaging may underestimate the proportion of patients with normal, symmetric ligaments. This study demonstrates that high-field 3-T MRI provides better visualization of the alar ligaments compared with 1.5-T MRI. The higher signal-to-noise ratio allows detection of small signal changes. A great interindividual variety of the MRI morphology of the alar ligaments was found in participants with no history of neck trauma. Further studies with more participants are necessary to evaluate alar ligament pathologies in patients with a history of whiplash injury.