Frequency of deep-seated cerebral microbleeds in patients with lobar hemorrhages and histopathological evidence for cerebral amyloid angiopathy

BackgroundCerebral amyloid angiopathy (CAA) is a common disease and the most common cause of lobar hemorrhages in the elderly. Usually, deep-seated microhemorrhages preclude the diagnosis of CAA. In this study, we sought to estimate the frequency of deep-seated microbleeds on MRI in patients with lobar hemorrhages and histopathological evidence for cerebral amyloid angiopathy. In addition, we describe a cohort of patients with cortical and deep-seated microbleeds on MRI and a histopathological specimen available from lobar hematoma evacuation.MethodsRetrospective database search for histopathological specimens from lobar hematoma evacuation and review of imaging findings (CT and MRI) and patient charts was performed.ResultsBetween 1 January 2012 and 31 December 2020, 88 specimens from 88 patients were available. A total of 56 specimens were excluded (no brain tissue in the specimen n = 4, other diagnosis n = 8, no MRI n = 43, and no BOLD-based sequence n = 1). Of the remaining 32 patients, 25 patients (78%) did not harbor deep-seated lesions on MRI, of which 17 patients had histopathological features of CAA. A total of seven patients harbored deep-seated CMB. Of these seven patients, three (3/20, 15%) had histopathological features of CAA.ConclusionApproximately 15% of patients with histopathologically diagnosed CAA harbor deep-seated microbleeds. This finding may add to the discussion on how to identify patients with CAA and deep-seated CMB

TAMEP are brain tumor parenchymal cells controlling neoplastic angiogenesis and progression

Aggressive brain tumors like glioblastoma depend on support by their local environment and subsets of tumor parenchymal cells may promote specific phases of disease progression. We investigated the glioblastoma microenvironment with transgenic lineage-tracing models, intravital imaging, single-cell transcriptomics, immunofluorescence analysis as well as histopathology and characterized a previously unacknowledged population of tumor-associated cells with a myeloid-like expression profile (TAMEP) that transiently appeared during glioblastoma growth. TAMEP of mice and humans were identified with specific markers. Notably, TAMEP did not derive from microglia or peripheral monocytes but were generated by a fraction of CNS-resident, SOX2-positive progenitors. Abrogation of this progenitor cell population, by conditional Sox2-knockout, drastically reduced glioblastoma vascularization and size. Hence, TAMEP emerge as a tumor parenchymal component with a strong impact on glioblastoma progression

Association of ABC-transporter variant with the risk of Alzheimer`s disease

Einige Studien weisen darauf hin, dass die ABC-Transporter ABCB1 (P-Glykoprotein, P-gp) und ABCG2 (breast cancer resistance protein, BCRP) aktiv Abeta transportieren und so maßgeblich zur Entstehung einer Alzheimerdemenz beitragen. Da die Transportaktivität vieler ABC-Transporter unter anderem durch genetische Polymorphismen (SNPs) moduliert wird, untersuchten wir den Einfluss ausgewählter SNPs der Gene für ABCA1, ABCB1, ABCC2 und ABCG2 in cerebralen DNA-Proben histopathologisch gesichtert an Alzheimerdemenz erkrankter Personen im Vergleich zu gesunden Kontrollen.A number of studies have demonstrated that the ATP-binding cassette (ABC) transporters P-glykoprotein (P-gp, ABCB1) and the breast cancer resistance protein (BCRP, ABCG2) actively transport beta-amyloid, thereby possibly contributing to the risk of Alzheimer`s disease (AD). Since the function of P-gp may be modulated by genetic polymorphisms, we investigated the relationship between single nucleotide polymorphisms (SNPs) of selected multidrug transporter genes (here examined ABCA1, ABCB1, ABCC2 and ABCG2)in histopathologically confirmed AD cases in comparison with controls

Tests for dementia diagnosis for patients with a migratory background

Die Beurteilung des kognitiven Zustandes eines Patienten mit Migrationshintergrund bedeutet für einen Untersucher, der dessen Muttersprache nicht beherrscht, eine diagnostische Herausforderung. Werden gängige Testverfahren angewendet, produzieren diese zu viele falsch positive Ergebnisse. Die beiden wichtigsten Gründe hierfür sind einerseits die hohe Sprachlast der herkömmlichen Instrumente und das im Vergleich zur gleichaltrigen deutschstämmigen Bevölkerung und somit zur Normstichprobe deutlich niedrigere Bildungsniveau der in Deutschland lebenden älteren Migranten. In der vorliegenden Arbeit wurde die Eignung von sechs sprachfreien Testverfahren zur Demenzdiagnostik für Patienten mit Migrationshintergrund durch einen deutschsprachigen Untersucher unter besonderer Berücksichtigung von Deutschkenntnissen und Bildungsniveau überprüft. Angewendet wurden Tests des averbalen Gedächtnis (Kopie und Reproduktion einer einfachen abstrakten Figur sowie Wiedererkennen von Figurenpaaren), der zeitlichen Orientierung (Multiple Choice Version), der Apraxie (Uhrentest und Hand-Faust-Sequenzen) sowie logische Reihen aus dem LPS 50+ (Untertest 3). In verschiedenen haus- und nervenärztlichen Praxen sowie in kultursensiblen Pflegeeinrichtungen wurden Migranten ab 60 Jahren mit den ausgewählten Testverfahren untersucht. Entsprechend der Einschätzung der behandelnden Ärzte wurden sie der Demenz- (n=30) oder der Kontrollgruppe (n=33) zugeordnet. In beiden Gruppen waren überwiegend türkischstämmige Patienten (je 80%) mit sehr niedriger formaler Bildung (3 Schuljahre in der Demenzgruppe, 4 in der Kontrollgruppe, n.s.). Der Anteil derer, die mangelhaft deutsch sprach, war hoch (Demenzgruppe 57 %, Kontrollgruppe 27 %, p<0,05), ebenso der Anteil der Analphabeten (Demenzgruppe 40%, Kontrollgruppe 18%, p<0,05). Statistisch zeigen die Ergebnisse signifikante Unterschiede zwischen den Diagnosegruppen bei allen untersuchten Testverfahren, allerdings sind die Parameter der diagnostischen Relevanz unterschiedlich und teilweise nur befriedigend. Lediglich ein Subtest (Figurenpaare Wiedererkennen) erscheint auch aus Gründen der Praktikabilität nicht geeignet. Für Patienten mit mangelhaften Deutschkenntnissen kann die Eignung nur für eine Auswahl der untersuchten Testverfahren nachgewiesen werden. Eine Untersuchung an einer größeren Stichprobe ist wünschenswert. Bei Analphabeten gelingt eine Einschätzung des kognitiven Zustandes mittels der untersuchten Verfahren nicht. Zusammenfassend stehen mit den Testverfahren Instrumente zur Verfügung, die eine orientierende Einschätzung des kognitiven Zustandes von Patienten mit Migrationshintergrund auch durch einen nicht- muttersprachlichen Untersucher erlauben. Im Hinblick auf dementielle Erkrankungen leisten die Testverfahren einen Beitrag zur Verbesserung der Basisversorgung der älteren Migranten.The cognitive assessment of patients with a migratory background is a challenge for an examiner who does not speak the patient’s mothertongue. Standard instruments produce too many false-positive results. The two most important reasons for this are on the one hand that common instruments are highly language-based and on the other hand that the elder immigrants in Germany have a much lower level of education compared to the same-age German population and thus to the standard sample. In this study six non-verbal tests were examined for their ability to detect dementia in patients with a migratory background by an examiner who only speaks German accounting especially for patients’ German language skills and education. Tests of the non-verbal memory (a simple abstract figure for copy and reconstruction from memory and recognizing pairs of figures), the temporal orientation (multiple choice version), the apraxia (clock-drawing test and hand-fist-sequences) along with logical sequences (odds-out, LPS 50+ subtest 3) were used. In physicians’ and psychiatric outpatient departments as well as in culture- sensitive care departments immigrants older than 60 years were examined with the collection of tests. According to the evaluation of their physician or psychiatrist they were assigned to the dementia (n=30) or the control group (n=33). In both groups were mostly subjects of Turkish origin (each 80%) with very low formal education (3 years in the dementia group, 4 years in the control group, ns). Poor German language skills were common (57% in the dementia group, 27% in the control group, p<0,05), as was analphabetism (dementia group 40%, control group 18, p<0,05). Statistically the results show significant differences between the two groups in all tests, but the markers for the diagnostic relevance differ and are partly only moderate. Only one subtest (recognizing pairs of figures) fails also due to its inpracticality. For patients with poor German language skills only a selection of tests seem appropriate. A study with a larger sample would be helpful. For analphabets the tests were not suitable. In summary a basic instrument for the detection of dementia in patients with a migratory background is provided which helps to improve basic health care for these patients

Challenges in the analysis of longitudinal pain data : practical lessons from a randomized trial of annular closure in lumbar disc surgery

Purpose: To analyze leg pain severity data from a randomized controlled trial (RCT) of lumbar disc surgery using integrated approaches that adjust pain scores collected at scheduled follow-up visits for confounding clinical events occurring between visits. Methods. Data were derived from an RCT of a bone-anchored annular closure device (ACD) following lumbar discectomy versus lumbar discectomy alone (Control) in patients with large postsurgical annular defects. Leg pain was recorded on a 0 to 100 scale at 6 weeks, 3 months, 6 months, 1 year, and 2 years of follow-up. Patients with pain reduction ≥20 points relative to baseline were considered responders. Unadjusted analyses utilized pain scores reported at follow-up visits. Since symptomatic reherniation signifies clinical failure of lumbar discectomy, integrated analyses adjusted pain scores following a symptomatic reherniation by baseline observation carried forward for continuous data or classification as nonresponders for categorical data. Results: Among 550 patients (272 ACD, 278 Control), symptomatic reherniation occurred in 10.3% of ACD patients and in 21.9% of controls (p < 0.001) through 2 years. There was no difference in leg pain scores at the 2-year visit between ACD and controls (12 versus 14; p = 0.33) in unadjusted analyses, but statistically significant differences favoring ACD (19 versus 29; p < 0.001) in integrated analyses. Unadjusted nonresponder rates were 6.0% with ACD and 6.7% with controls (p = 0.89), but 15.7% and 27.8% (p = 0.001) in integrated analyses. The probability of nonresponse was 16.4% with ACD and 18.3% with controls (p = 0.51) in unadjusted analysis, and 23.7% and 31.2% (p = 0.04) in integrated analyses. Conclusion: In an RCT of lumbar disc surgery, an integrated analysis of pain severity that adjusted for the confounding effects of clinical failures occurring between follow-up visits resulted in different conclusions compared to an unadjusted analysis of pain scores reported at follow-up visits only

Clinical and radiological differences between patients with probable cerebral amyloid angiopathy and mixed cerebral microbleeds

Background!#!The key imaging features of cerebral amyloid angiopathy (CAA) are lobar, cortical, or cortico-subcortical microbleeds, macrohaemorrhages and cortical superficial siderosis (cSS). In contrast, hypertensive angiopathy is characterized by (micro) haemorrhages in the basal ganglia, thalami, periventricular white matter or the brain stem. Another distinct form of haemorrhagic microangiopathy is mixed cerebral microbleeds (mixed CMB) with features of both CAA and hypertensive angiopathy. The distinction between the two entities (CAA and mixed CMB) is clinically relevant because the risk of haemorrhage and stroke should be well balanced if oral anticoagulation is indicated in CAA patients. We aimed to comprehensively compare these two entities.!##!Methods!#!Patients with probable CAA according to the modified Boston criteria and mixed CMB without macrohaemorrhage were retrospectively identified from our database. Comprehensive comparison regarding clinical and radiological parameters was performed between the two cohorts.!##!Results!#!Patients with CAA were older (78 ± 8 vs. 74 ± 9 years, p = 0.036) and had a higher prevalence of cSS (19% vs. 4%, p = 0.027) but a lower prevalence of lacunes (73% vs. 50%, p = 0.018) and deep lacunes (23% vs. 51%, p = 0.0003) compared to patients with mixed CMB. Logistic regression revealed an association between the presence of deep lacunes and mixed CMB. The other collected parameters did not reveal a significant difference between the two groups.!##!Conclusions!#!CAA and mixed CMB demonstrate radiological differences in the absence of macrohaemorrhages. However, more clinically available biomarkers are needed to elucidate the contribution of CAA and hypertensive angiopathy in mixed CMB patients

Effectiveness of an Annular Closure Device to Prevent Recurrent Lumbar Disc Herniation: A Secondary Analysis with 5 Years of Follow-up

Importance: Patients with large annular defects following lumbar microdiscectomy for disc herniation are at increased risk for symptomatic recurrence and reoperation. Objective: To determine whether a bone-anchored annular closure device in addition to lumbar microdiscectomy resulted in lower reherniation and reoperation rates vs lumbar microdiscectomy alone. Design, Setting, and Participants: This secondary analysis of a multicenter randomized clinical trial reports 5-year follow-up for enrolled patients between December 2010 and October 2014 at 21 clinical sites. Patients in this study had a large annular defect (6-10 mm width) following lumbar microdiscectomy for treatment of lumbar disc herniation. Statistical analysis was performed from November to December 2020. Interventions: Lumbar microdiscectomy with additional bone-anchored annular closure device (device group) or lumbar microdiscectomy only (control group). Main Outcomes and Measures: The incidence of symptomatic reherniation, reoperation, and adverse events as well as changes in leg pain, Oswestry Disability Index, and health-related quality of life when comparing the device and control groups over 5 years of follow-up. Results: Among 554 randomized participants (mean [SD] age: 43 [11] years; 327 [59%] were men), 550 were included in the modified intent-to-treat efficacy population (device group: n = 272; 270 [99%] were White); control group: n = 278; 273 [98%] were White) and 550 were included in the as-treated safety population (device group: n = 267; control group: n = 283). The risk of symptomatic reherniation (18.8% [SE, 2.5%] vs 31.6% [SE, 2.9%]; P <.001) and reoperation (16.0% [SE, 2.3%] vs 22.6% [SE, 2.6%]; P =.03) was lower in the device group. There were 53 reoperations in 40 patients in the device group and 82 reoperations in 58 patients in the control group. Scores for leg pain severity, Oswestry Disability Index, and health-related quality of life significantly improved over 5 years of follow-up with no clinically relevant differences between groups. The frequency of serious adverse events was comparable between the treatment groups. Serious adverse events associated with the device or procedure were less frequent in the device group (12.0% vs 20.5%; difference, -8.5%; 95% CI, -14.6% to -2.3%; P =.008). Conclusions and Relevance: In patients who are at high risk of recurrent herniation following lumbar microdiscectomy owing to a large defect in the annulus fibrosus, this study's findings suggest that annular closure with a bone-anchored implant lowers the risk of symptomatic recurrence and reoperation over 5 years of follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT01283438

sj-jpg-6-wso-10.1177_17474930231152124 – Supplemental material for Characterizing mixed location hemorrhages/microbleeds with CSF markers

Supplemental material, sj-jpg-6-wso-10.1177_17474930231152124 for Characterizing mixed location hemorrhages/microbleeds with CSF markers by Ulf Jensen-Kondering, Nils G Margraf, Caroline Weiler, Walter Maetzler, Justina Dargvainiene, Kim Falk, Sarah Philippen, Thorsten Bartsch, Charlotte Flüh, Christoph Röcken, Bettina Möller, Georg Royl, Alexander Neumann, Norbert Brüggemann, Benjamin Roeben, Claudia Schulte, Benjamin Bender, Daniela Berg and Gregor Kuhlenbäumer in International Journal of Stroke</p