Christian Foerch

Frontotemporal lobar degeneration (FTLD) can present as a behavioral or language variant (bvFTLD or a primary progressive aphasia [PPA], or as a syndrome with parkinsonism, such as corticobasal syndrome [CBS] or progressive supranuclear palsy [PSP]). The incidence of FTLD varies in epidemiologic studies, reaching 3 per 100,000 person-years. Only few data exist regarding survival times. We evaluated incidence and survival rates in a population-based registry with high coverage in Southern Germany. The epidemiologic ALS-FTLD registry Swabia covers a population of 8.4 million inhabitants in south-west Germany. Raw and age-standardized incidence rates, as well as incidence rate ratios (IRR) with 95% CIs were calculated. Median survival time was estimated for different FTLD variants using the Kaplan-Meier method. Between 2015 and 2022, 515 patients with FTLD (mean age at diagnosis 68.0 ± 9.5 years, 59.8% men) were registered. The median diagnostic delay was 24.8 months. The most common variant was bvFTLD (n = 185, 35.9%; 66.5% men), followed by PPA (n = 147, 28.5%; 51.0% men), PSP (n = 133, 25.8%; 62.9% men), and CBS (n = 22, 4.3%; 50% men). The overall FTLD incidence was 0.77 (95% CI 0.71-0.84), and the age-standardized incidence was 0.76 (95% CI 0.69-0.82) per 100.000 person-years. The age-standardized incidence was higher in men than in women, with an IRR of 1.73 (95% CI 1.44-2.00). In men, incidence increased from the age 50 years, primarily due to bvFTD, whereas in women this rise was primarily due to PSP. The median survival (N = 392) from diagnosis was 53.6 months (95% CI 50.9-62.0) overall, 73.1 months (95% CI 63.6-82.8) for patients with PPA, 42.8 months (95% CI 35.1-64.3) for patients with bvFTD, and 49.5 months (95% CI 39.2-53.7) for patients with PPS/CBS. We observed a raw incidence rate of 0.77, thus considerably lower than in most previous reports. Incidence was substantially higher in men than in women. The prognosis from the time of diagnosis depended highly on the specific FTLD subtype. Our data are based on the large sample size and high capture rate of a central European population-based registry.

The rapid identification of intracerebral hemorrhage (ICH) in patients with symptoms of acute stroke is decisive for prehospital triage and initiation of targeted therapies. Glial fibrillary acidic protein (GFAP) is a highly promising blood-biomarker indicating ICH. In this study, we investigated the potential of a new GFAP test run on a point-of-care platform for distinguishing ICH from ischemic stroke (IS) and stroke mimics (SM) in the prehospital phase. This prospective diagnostic accuracy study was conducted at the RKH Klinikum Ludwigsburg, a tertiary care hospital in Baden-Württemberg, Germany. Patients with symptoms of acute stroke admitted within 6 hours of symptom onset were enrolled. Blood samples were collected in the prehospital phase. Plasma GFAP measurements were performed on the i-STAT-Alinity device (duration: 15 minutes) in-hospital. The gold standard was the final diagnosis categorized ICH, IS, or SM. A total of 353 patients were enrolled (mean age 74.6 ± 13.4 years; 46.7% female). GFAP concentrations were elevated in patients with ICH (n = 76; median 208 pg/mL [interquartile range 60-5,907]) compared with IS (n = 258; 30 pg/mL [29-51]) and SM (n = 19; 48 pg/mL [29-97]; p < 0.001). The optimal GFAP cutoff point to differentiate ICH from IS and SM was 55 pg/mL (area under the curve of 0.880, 95% CI 0.834-0.925, p < 0.001). IS and SM GFAP levels slightly increased in parallel with increasing age. Hence, different GFAP cutoff points were determined to identify ICH across 3 age groups with moderate to high positive predictive values (PPVs) (90.0%-95.5%; minimum lower CI 55.0%, maximum upper CI 99.3%) (sensitivity values 56.3%-72.4%, specificity values 98.9%-99.0% and negative predictive values [NPVs] 87.5%-92.7%). Vice versa, in patients with a moderate to severe neurologic deficit (NIH Stroke Scale >6), GFAP values <30 pg/mL ruled out ICH with a NPV of 100.0%. Laboratory GFAP measurements on a point-of-care platform in blood samples collected from patients with symptoms of acute stroke in the prehospital phase can help to identify ICH with moderate to high PPV. Following confirmation in larger independent cohorts using optimized eligibility criteria and validated age-specific cutoff values, GFAP testing could facilitate optimized triage and the initiation of blood pressure-lowering therapy and anticoagulation reversal in earlier time frames. This study provides Class II evidence that elevated plasma GFAP levels within 6 hours of symptom onset accurately distinguish patients with ICH from IS and SM.

BACKGROUND: Atrial fibrillation detected after stroke (AFDAS) affects secondary stroke prevention, yet identification can be challenging. Easily accessible cardiac blood biomarkers such as NT-proBNP (N-terminal pro-B-type natriuretic peptide) could guide diagnostic workup, but optimal cutoff values and the time-dependent relationship between NT-proBNP and AFDAS are unclear. We aimed (1) to externally validate earlier presented NT-proBNP cutoffs for atrial fibrillation prediction and (2) to assess the time-dependent relationship of NT-proBNP and early in-hospital AFDAS versus AFDAS after discharge. METHODS: We conducted a pooled data analysis of patients with ischemic stroke from the prospective international multicenter BIOSIGNAL (Biomarker Signature of Stroke Aetiology) cohort study (European Stroke Centers from October 2014 to October 2017) and the prospective single-center Graz stroke pathway study (Austria from May 2018 to August 2020). AFDAS was defined as ≥30-s atrial fibrillation/flutter diagnosed within 1 year post-admission and categorized in in-hospital versus after discharge. NT-proBNP was assessed ≤24 hours of symptom onset. The association between NT-proBNP and AFDAS was evaluated by a multivariable logistic regression analysis. RESULTS: AFDAS was diagnosed in 374 (16%) of 2292 patients with ischemic stroke (median age, 74 years; 42% female), 268 (72%) during hospitalization, and 106 (28%) after discharge (median duration of hospitalization, 15 days). NT-proBNP levels at admission had a good predictive capacity for in-hospital AFDAS (area under the receiver operating characteristic curve, 0.83 [95% CI, 0.81–0.86]). For patients diagnosed with AFDAS after discharge, the predictive capacity of NT-proBNP was poor (area under the receiver operating characteristic curve, 0.65 [95% CI, 0.60–0.70]), and 20% had normal NT-proBNP values <125 pg/mL at admission. The NT-proBNP cutoff of 505 pg/mL exhibited high sensitivity (82%) and specificity (71%) for in-hospital AFDAS, with a negative predictive value of 96%. CONCLUSIONS: In patients with ischemic stroke, the admission NT-proBNP cutoff of 505 pg/mL seems to be a reliable predictor for in-hospital AFDAS, while the predictive capacity of NT-proBNP for AFDAS after discharge is limited. Our results might influence the designs of future secondary stroke prevention trials.

Background: A strong risk factor for intracerebral hemorrhage (ICH) is elevated arterial blood pressure, which is known to vary by season, with highest values in winter months. The objective was to assess seasonal trends of ICH incidence, clinical severity, and case fatality according to demographic and clinical characteristics. Methods: This study was conducted on adult patients hospitalized for ICH between 2003 and 2022. Cases were identified from a stroke inpatient quality assurance registry covering the entire Federal State of Hesse, Germany. Population data were derived from the Hessian Bureau of Statistics. Incidence rates (IRs) per 100 000 person‐years of ICH, recorded with 4‐digit International Statistical Classification of Diseases, Tenth Revision, German Modification ( ICD‐10‐GM ) I61.x codes, were estimated by season, calendar month, and bleeding location. Seasonal variations and subgroup analyses were tested using Poisson distribution and the Wald test. Results: A total of 33 444 patients were included (mean age, 72.4±13.6 years, 52% men). ICH IR correlated with the season of occurrence, demonstrating a peak in winter (IR winter, 34.6 [95% CI, 33.9–35.4], IR summer, 29.4 [95% CI, 28.7–30.1]; P P P <0.01). Clinical severity and case fatality did not vary between seasons (mean, 24.3±0.8%). Conclusions: This large cohort study demonstrates a seasonal incidence peak of ICH in winter. Whether ICH can be prevented by better control of arterial blood pressure in seasons with expected incidence peaks will require further studies.

Impaired renal function can influence biomarker levels through mechanisms involving blood–brain barrier integrity and clearance pathways; however, the impact of variations within normal renal function remains unclear. The main aim of this study was to determine whether adjustment for the specific level of renal function is necessary when renal function remains within physiological levels. We studied n = 183 patients (NID n = 122; other neurological diseases n = 39; somatoform controls n = 22) who underwent lumbar puncture at University Hospital Frankfurt. Serum and cerebrospinal fluid (CSF) levels of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total tau protein (tTAU), and ubiquitin C-terminal hydrolase-L1 (UCHL1) were measured using the single molecule array (SIMOA) technique. Estimated glomerular filtration rate (eGFR) correlated negatively with CSF GFAP (r = −0.217, p = 0.004) and serum NfL (r = −0.164, p = 0.032). Patients with impaired renal function exhibited higher CSF NfL (p = 0.036) and CSF GFAP (p = 0.026) levels. However, these findings did not remain significant after adjusting for BMI and age. Importantly, in patients with normal renal function, no significant correlations with eGFR and biomarker levels were observed after adjustment. Our findings indicate that serum and CSF concentrations of NfL, GFAP, tTAU, and UCHL1 are not significantly affected by fluctuations in physiological kidney function but emphasize the importance of considering comorbidities in impaired renal function when interpreting biomarker levels.

Prolonged cardiac monitoring (PCM) increases atrial fibrillation (AF) detection after ischemic stroke, but access is limited, and it is burdensome for patients. Our objective was to assess whether midregional proatrial natriuretic peptide (MR-proANP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) could classify people who are unlikely to have AF after ischemic stroke and allow better targeting of PCM. We analyzed people from the Biomarker Signature of Stroke Aetiology (BIOSIGNAL) study with ischemic stroke, no known AF, and ≥3 days cardiac monitoring. External validation was performed in the Preventing Recurrent Cardioembolic Stroke: Right Approach, Right Patient (PRECISE) study of 28 days of cardiac monitoring in people with ischemic stroke or transient ischemic attack and no known AF. The main outcome is no AF detection. We assessed the discriminatory value of MR-proANP and NT-proBNP combined with clinical variables to identify people with no AF. A decision curve analysis was performed with combined data to determine the net reduction in people who would undergo PCM using the models based on a 15% threshold probability for AF detection. We included 621 people from the BIOSIGNAL study. The clinical multivariable prediction model included age, NIH Stroke Scale score, lipid-lowering therapy, creatinine, and smoking status. The area under the receiver-operating characteristic curve (AUROC) for clinical variables was 0.68 (95% CI 0.62-0.74), which improved with the addition of log₁₀MR-proANP (0.72, 0.66-0.78; p = 0.001) or log₁₀NT-proBNP (0.71, 0.65-0.77; p = 0.009). Performance was similar for the models with log₁₀MR-proANP vs log₁₀NT-proBNP (p = 0.28). In 239 people from the PRECISE study, the AUROC for clinical variables was 0.68 (0.59-0.76), which improved with the addition of log₁₀NT-proBNP (0.73, 0.65-0.82; p < 0.001) or log₁₀MR-proANP (0.79, 0.72-0.86; p < 0.001). Performance was better for the model with log₁₀MR-proANP vs log₁₀NT-proBNP (p = 0.03). The models could reduce the number of people who would undergo PCM by 30% (clinical and log₁₀MR-proANP), 27% (clinical and log₁₀NT-proBNP), or 20% (clinical only). MR-proANP and NT-proBNP help classify people who are unlikely to have AF after ischemic stroke. Measuring MR-proANP or NT-proBNP could reduce the number of people who need PCM by 30%, without reducing the amount of AF detected. NCT02274727; clinicaltrials.gov/study/NCT02274727.

Background and purpose: Although the Boston criteria version 2.0 facilitates the sensitivity of cerebral amyloid angiopathy (CAA) diagnosis, there are only limited data about precursor symptoms. This study aimed to determine the impact of neurological and imaging features in relation to the time of CAA diagnosis.Methods: Patients diagnosed with probable CAA according to the Boston criteria version 1.5, treated between 2010 and 2020 in our neurocentre, were identified through a keyword search in our medical database. Neuroimaging was assessed using Boston criteria versions 1.5 and 2.0. Medical records with primary focus on the clinical course and the occurrence of transient focal neurological episodes were prospectively evaluated.Results: Thirty‐eight out of 81 patients (46.9%) exhibited transient focal neurological episodes, most often sensory (13.2%) or aphasic disorders (13.2%), or permanent deficits at a mean time interval of 31.1 months (SD ±26.3; range 1–108 months) before diagnosis of probable CAA (Boston criteria version 1.5). If using Boston criteria version 2.0, all patients receiving magnetic resonance imaging (MRI) met the criteria for probable CAA, and diagnosis could have been made on average 44 months earlier. Four patients were younger than 50 years, three of them with supporting pathology. Cognitive deficits were most common (34.6%) at the time of diagnosis.Conclusions: Non‐haemorrhagic MRI markers enhance the sensitivity of diagnosing probable CAA; however, further prospective studies are proposed to establish a minimum age for inclusion. As the neurological overture of CAA may occur several years before clinical diagnosis, early clarification by MRI including haemosensitive sequences are suggested.

Background. Factor VII activating protease (FSAP) is a circulating serine protease that could be involved in the pathophysiology of stroke. We analyzed the temporal changes in FSAP antigen and FSAP activity after acute cerebral ischemia (ACI) and tested if FSAP could be used to differentiate between stroke subtypes in the hyperacute phase (Methods. Of the 118 suspected stroke patients enrolled, 76 had ACI; of which 20 suffered from large vessel occlusion (LVO), 19 had intracerebral hemorrhage (ICH), and 23 had stroke mimics. Median time from symptom onset to the two plasma sample collections, ). FSAP antigen, FSAP activity, FSAP-α2-antiplasmin-complex (FSAP-AP complex), and nucleosomes were measured by activity assays or ELISA. Results. ACI patients treated with tissue plasminogen activator (tPA) had elevated FSAP hours ( ) that subsequently normalized after 6 hours. FSAP-AP complex levels decreased significantly from ) to 6 hours after symptom onset. tPA did not increase FSAP activity significantly in plasma in vitro. FSAP antigen significantly hours after symptom onset in LVO ( ) and ICH ( ) patients. FSAP could not differentiate ACI from ICH or strokes (ACI and ICH) from stroke mimics. FSAP did not correlate with stroke severity. Conclusion. LVO and ICH seem to influence FSAP levels in the hyperacute phase of stroke, but FSAP does not differentiate between stroke subtypes in a hyperacute setting.

(Background): Effective prevention strategies and acute therapies have been established and distributed in recent years to reduce the global burden of stroke. However, beyond randomized clinical trials, limited data exist on the real-world impact of these measures. Our goal was to analyze whether the stroke-associated disability in the population decreased over time based on a state-wide stroke registry analysis. (Methods): Consecutive data from a state-wide inpatient stroke registry covering the entire federal state of Hesse, Germany, were obtained. The clinical data of 141,287 patients with ischemic stroke (ICD-10: I63) admitted between 2010 and 2019 were included. The primary outcome was the odds ratio for a change of modified Ranking Scale (mRS) at discharge over time, estimated by ordinary logistic regression and adjusted for age and sex. The secondary outcome was the odds ratio for a lower National Institutes of Health Stroke Scale (NIHSS) score at hospital admission. (Results): The absolute number of severely disabled (mRS 4–5) stroke patients at discharge decreased over time (2010: 3223 (equivalent to 53/100,000 population); 2019: 2429 [39/100,000 population]). The odds at hospital admission for a higher mRS at discharge decreased significantly by 3.7% per year (OR 0.963 (95% CI 0.960–0.966), p < 0.001). The absolute number of severely affected stroke patients (NIHSS > 15) at admission declined over time (2010: 1589 [26/100,000]; 2019: 1185 [19/100,000]; p < 0.001). The odds for a higher NIHSS score at admission to hospital decreased by 3.8% per year (OR 0.962 (95% CI 0.959–0.965), p < 0.001). Trends were most prominent for patients aged 80 years and older and for patients with atrial fibrillation but absent in patients <60 years. (Conclusions): Stroke-associated disability in the population steadily decreased between 2010 and 2019. The improved prevention of severe strokes in elderly patients may be a major driver of this observation.

Purpose: We aimed to re-evaluate the relationship between thalamic infarct (TI) localization and clinical symptoms using a vascular (VTM) and a novel functional territorial thalamic map (FTM). Methods: Magnetic resonance imaging (MRI) and clinical data of 65 patients with isolated TI were evaluated (female n = 23, male n = 42, right n = 23, left n = 42). A VTM depicted the known seven thalamic vascular territories (VT: inferolateral, anterolateral, inferomedial, posterior, central, anteromedian, posterolateral). An FTM was generated from a probabilistic thalamic nuclei atlas to determine six functionally defined territories (FT: anterior: memory/emotions; ventral: motor/somatosensory/language; medial: behavior/emotions/nociception, oculomotor; intralaminar: arousal/pain; lateral: visuospatial/somatosensory/conceptual and analytic thinking; posterior: audiovisual/somatosensory). Four neuroradiologists independently assigned diffusion-weighted imaging (DWI) lesions to the territories mapped by the VTM and FTM. Findings were correlated with clinical features. Results: The most frequent symptom was a hemisensory syndrome (58%), which was not specific for any territory. A co-occurrence of hemisensory syndrome and hemiparesis had positive predictive values (PPV) of 76% and 82% for the involvement of the inferolateral VT and ventral FT, respectively. Thalamic aphasia had a PPV of 63% each for involvement of the anterolateral VT and ventral FT. Neglect was associated with involvement of the inferolateral VT/ventral FT. Interrater reliability for the assignment of DWI lesions to the VTM was fair (κ = 0.36), but good (κ = 0.73) for the FTM. Conclusion: The FTM revealed a greater reproducibility for the topographical assignment of TI than the VTM. Sensorimotor hemiparesis and neglect are predictive for a TI in the inferolateral VT/ventral FT. The hemisensory syndrome alone does not allow any topographical assignment.